A Study to Investigate the Safety and Efficacy of Ripasudil (K-321) Eye Drops After Descemetorhexis in Patients with Fuchs Endothelial Corneal Dystrophy

Phase 1

Conditions: In Fuchs endothelial corneal dystrophy (FECD), there is an increased rate of loss of endothelial cells, starting in the centre of Descemet’s membrane and spreading to the periphery, resulting in excrescences known as guttae, which are a marker of the condition. Guttae may coalesce and inhibit the migration of endothelial cells. Eventually the corneal endothelium ceases to function effectively, and the cornea begins to cloud, leading eventually to blindness.
MedDRA version: 20.0Level: LLTClassification code 10014823Term: Endothelial corneal dystrophySystem Organ Class: 100000004850
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2019-003280-22-DK

Lead Sponsor: Kowa Research Institute, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

Each patient must meet all of the following criteria to be enrolled in this study:
1. Is at least 18 years old at the screening visit (Visit 1). Re-screening possible if initial screening was soon before 18th birthday.
2. Has a diagnosis of FECD at Visit 1. Rescreening is not possible.
3. Has confluent central guttae in the study eye that can be removed by descemetorhexis of a circular area of 5 mm diameter or less (at Visit 1). Rescreening is not possible.
4. Has a study eye with best corrected visual acuity (BCVA) of 75 letters or fewer by Early Treatment Diabetic Retinopathy Study (ETDRS) testing (Snellen equivalent of 20/32 or worse) at Visit 1. Rescreening is not possible.
5. The study eye descemetorhexis at Visit 2 is confirmed to have excised a central area with confluent guttae and a diameter of 4.5 to 5.5 mm. Guidance for performing the study eye descemetorhexis and measurement of the excised area will be provided in the study manual. Rescreening is not possible in that eye but the non-study eye can be used.
6. Can understand the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements before any study-specific assessment is performed. Rescreening is not possible.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Patients meeting any of the following criteria will be excluded from the study:
1. Is a female patient and any of the following is true:
• is pregnant or lactating/breastfeeding, or
• is not surgically sterile, not post-menopausal (no menses for the previous 12 months), or not practising an effective method of birth control as determined by the investigator (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy).
If a patient is female and of childbearing potential, she must have a negative urine
pregnancy test result at Visit 2 before the descemetorhexis. Women of childbearing potential must also agree to use effective contraception throughout the study. A female of childbearing potential is defined as a woman who has experienced menarche and has not undergone successful surgical sterilisation or is not post-menopausal, and a post-menopausal woman is defined as having had no menses for the previous 12 months (without a known cause). Rescreening is possible if patient either stops nursing or initiates birth control.
2. Has a study eye with confluent guttae in the periphery or confluent guttae outside the stripped area (individual guttae are allowed). Note that patients may have individual or small number of guttae remaining outside the stripped area, but there should be no areas of confluent guttae remaining after the descemetorhexis. For example, a patient who had 5 to 10 guttae remaining in a few spots around the circumference of the descemetorhexis would not be excluded by this criterion. Rescreening is not possible.
3. Has a study eye with a history of cataract surgery within 90 days of Visit 1. Rescreening is possible.
4. Has a study eye with a history of any previous ocular surgery other than for cataract. Rescreening is not possible.
5. Has a non-study eye with a history of any previous ocular surgery within 30 days of Visit 1. Rescreening is possible.
6. Plans to receive any surgical treatment on the study eye during any study period, other than the study descemetorhexis. Re-screening possible if during initial screening subject had plans for surgical treatment on the study eye during the study period, but upon re-screening these plans for surgery were cancelled.
7. Plans to receive any surgical treatment for FECD or cataract on the non-study eye in the screening or treatment period. – Re-screening possible if during initial screening subject had plans for surgical treatment for FECD or cataract on the non-study eye during the screening or treatment period, but upon re-screening these plans for surgery were cancelled.
8. Has advanced corneal stromal oedema defined as the presence of widespread haze or bullae on slit-lamp examination. Rescreening is not possible.
9. Has a study eye with central corneal thickness = 670 µm. Rescreening is not possible.
10. Has known severe comorbidities that may interfere with descemetorhexis (eg, a bacterial, viral, or fungal ophthalmic infection). Rescreening is not possible.
11. Has any clinically significant ocular condition other than FECD or cataract that requires medication or ocular surgery. Rescreening is not possible.
12. Has diabetes with poor blood sugar control (eg, HbA1c value > 8.5%). Rescreening possible if HbA1c has improved at the time of the re-screening.
13. Has used contact lenses within 7 days of Visit 1. Rescreening is possible.
14. Has hypersensitivity to any ophthalmic medicati

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to investigate the effect of K-321 dosed for 12 weeks on central ECD in patients with FECD after descemetorhexis.;Secondary Objective: The secondary objectives of this study are the following:<br>• to investigate the effect of K-321 on central ECD, corneal thickness, and corneal clarity in patients with FECD at each visit after descemetorhexis out to 52 weeks<br>• to assess the safety and tolerability of K-321 in patients with FECD at each visit after descemetorhexis out to 52 weeks;Primary end point(s): The primary efficacy endpoint is the central corneal ECD at Week 12 as assessed by the CIARC.;Timepoint(s) of evaluation of this end point: Week 12

Secondary Outcome Measures

Name	Time	Method

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