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 to blindness. MedDRA version: 20.0 Level: PT Classification co
Conditions
Sponsors
Kowa Research Institute, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Pre-DSO Criteria Each subject who is planning to undergo DSO must meet all of the following criteria to be enrolled in the study: 1. Is at least 18 years old at the screening visit (Visit 1) 2. Has a diagnosis of FECD at Visit 1 3. Has confluent central guttae in the study eye that can be removed by descemetorhexis of a circular area of 5.5 mm diameter or less (at Visit 1) 4. Study eye with BCVA of 75 letters or fewer by ETDRS testing (Snellen equivalent of 20/32 or worse) at Visit 1. 5. Can understand the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements before any study-specific assessments are performed. Post-DSO Criteria 6. 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. 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 46 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 54
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria will be excluded from the study: 1. Is a female subject of childbearing potential and any of the following is true: a. is pregnant or lactating/breastfeeding, or b. is not surgically sterile, not post-menopausal (no menses for the previous 12 months), or not practicing an effective method of birth control as determined by the Investigator [If a subject 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 sterilization 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)] 2. Has a study eye with confluent guttae in the periphery or confluent guttae outside the stripped area (individual guttae are allowed) after descemetorhexis (Note that subjects may have individual or a small number of guttae remaining outside the stripped area, but there should be no areas with confluent guttae remaining after the descemetorhexis. 3. Has a study eye with baseline (pre-DSO) peripheral ECD ungradable for any area (nasal, temporal, superior, and inferior) due to any reason other than a medical reason (eg, guttae, corneal edema, or striae) 4. Has a study eye with a history of cataract surgery within 90 days of Visit 1 5. Has a study eye with a history of any previous intraocular surgery other than for cataract prior to Visit 1 6. Has a non-study eye with a history of any previous intraocular surgery within 30 days of Visit 1 7. Plans to receive any surgical treatment on the study eye, other than the study descemetorhexis, during the duration of the study 8. Plans to receive any surgical treatment for FECD or cataract on the non-study eye during either the screening or treatment period 9. Has advanced corneal stromal edema, which is defined as the presence of widespread haze or bullae on slit lamp examination at Visits 1 and 2 10. Has a study eye with central corneal thickness = 670 µm at Visits 1 and 2 11. Has known severe comorbidities that may interfere with descemetorhexis (including but not limited to a bacterial, viral, or fungal ophthalmic infection) 12. Has any clinically significant ocular condition, other than FECD, cataract, primary open-angle glaucoma* or dry eye in the study eye that requires medication or ocular surgery (* Only primary open-angle glaucoma is allowed, NOT angle closure or any secondary glaucomas. Use of a single glaucoma medication, except for any carbonic anhydrase inhibitor [CAI] or ROCK inhibitor, is acceptable. Prior YAG-laser surgery is acceptable, but incisional surgery and micro invasive glaucoma surgery are not allowed.) 13. Has diabetes with poor blood sugar control, defined as hemoglobin A1c (HbA1c) value > 8.5% at Visit 1 14. Has used either collagen shield or contact lenses in either one eye or both eyes within 7 days of Visit 1 15. Is unwilling to stop use of either collagen shield or contact lenses for the duration of the study 16. Has hypersensitivity to any ophthalmic medication used for diagnosis or treatment, including eye drops containing antibiotic(s) or glucocorticoid(s) 17. Has known hypersensitivity to any component of the study drugs 18. Has previously used ripasudi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of K-321 on the time to improvement in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of =40 letters during the first 12 weeks after descemetorhexis in subjects with FECD.;Secondary Objective: The key secondary objective of this study is to investigate the effect of K-321 on: • The time to improvement in BCVA by ETDRS letter score of =20 letters. • The time to achievement of BCVA by ETDRS letter score of =70 letters. • Central corneal ECD. The secondary objectives (efficacy) of this study are to investigate the effect of K-321 on: • The time to complete clearance of corneal edema in both areas (epithelial, stromal) • The time to return of central corneal thickness to less than or equal to baseline level • The time to failure of therapy (defined as events of rescue treatments other than keratoplasty, study drug discontinuation due to lack of efficacy, and withdrawal from the study due to lack of efficacy) • On the time to undergo rescue therapy (keratoplasty) or rescue treatment. The secondary objective (safety) of this study is as follows: • To assess the safety and tolerability of K-321 in subjects with FECD after descemetorhexis.;Primary end point(s): The primary efficacy endpoint is the Time to =40 ETDRS letter improvement in BCVA during the first 12 weeks after descemetorhexis.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: • Time to =20 ETDRS letter improvement during the first 12 weeks after descemetorhexis. • Time to achievement of =70 ETDRS letters during the first 12 weeks after descemetorhexis. • Central corneal ECD change from baseline at Week 12. • Time to complete clearance of corneal edema in both areas (epithelial, stromal) during the first 12 weeks and during the 52-week period after descemetorhexis. • Time to return of central corneal thickness to less than or equal to baseline level during the first 12 weeks and during the 52-week period after descemetorhexis. • Time to failure of therapy (defined as events of rescue keratoplasty, rescue treatments other than keratoplasty, study drug discontinuation due to lack of efficacy, and withdrawal from the study due to lack of efficacy) during the 52-week period after descemetorhexis. • Time to undergo rescue therapy (keratoplasty) or rescue treatment during the 52-week period after descemetorhexis. ;Timepoint(s) of evaluation of this end point: Week 12 and Week 52 | — |
Countries
Canada, Denmark, Germany, Spain, United Kingdom, United States
Contacts
Public ContactKelsey Behrens
Kowa Research Institute, Inc.
Outcome results
None listed