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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kowa Research Institute Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

5 May 2023 → 20 Feb 2026

Decision date (initial)

2024-05-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-511752-40-00

EudraCT number

2021-006456-14

ClinicalTrials.gov

NCT05795699

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

The primary objective of this study is 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 Fuchs endothelial corneal dystrophy (FECD).

Secondary objectives 1

1. The key secondary objectives (efficacy) of this study are as follows: • To investigate the effect of K-321 on the time to improvement in BCVA by ETDRS letter score of ≥20 letters during the first 12 weeks after descemetorhexis. • To investigate the effect of K-321 on the time to achievement of BCVA by ETDRS letter score of ≥70 letters during the first 12 weeks after descemetorhexis. • To investigate the effect of K-321 on central corneal ECD at Week 12 after descemetorhexis. To investigate the effect of K-321 on the time to achievement of no corneal edema in both areas (epithelial, stromal) during the first 12 weeks after descemetorhexis. • To investigate the effect of K-321 on the time to exceed pre-DSO ETDRS letter score in BCVA during the first 12 weeks after descemetorhexis. Secondary objectives (efficacy) of this study are as follows: • To investigate the effect of K-321 on the time to achievement of no corneal edema in both areas (epithelial, stromal) during the 52-week period after descemetorhexis. • To investigate the effect of K-321 on the 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. • To investigate the effect of K-321 on the time to failure of therapy (defined as events of rescue keratoplasty, rescue treatments other than keratoplasty, study drug discontinuation before Week 12 (Visit 10) due to lack of efficacy, and withdrawal from the study due to lack of efficacy) during the 52-week period after descemetorhexis. • To investigate the effect of K-321 on the time to undergo rescue therapy (keratoplasty) or rescue treatment during the 52-week period after descemetorhexis. The key secondary objective (safety) of this study is as follows: • To assess the safety and tolerability of K-321 in subjects with FECD after descemetorhexis up to the end of the study (Week 52).

Conditions and MedDRA coding

Fuchs Endothelial Corneal Dystrophy

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002676-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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) 1) 4. Has either of the following visual impairments: a. Study eye with BCVA of 78 letters or fewer by ETDRS testing (Snellen equivalent of 20/32 or worse) at Visit 1, or b. Study eye with BCVA of greater than 78 letters by ETDRS testing and who have self-reported glare disability, or a reduction in vision due to a stray light (scattered light from a bright source, or self-reported difficulty with contrast sensitivity 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

Exclusion criteria 2

1. 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 (eg, oral contraceptives, double barrier methods, hormonal injectable or implanted contraceptives, tubal ligation, or partner with vasectomy) 2. Has a study eye with confluent guttae in the periphery or confluent guttae outside the stripped area (individual guttae are allowed) after 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 Visit 1 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 13. Has diabetes with poor blood sugar control, defined as hemoglobin A1c (HbA1c) value >8.5% at Visit 1
2. 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 the study eye within 7 days of Visit 1 15. Is unwilling to stop use of either collagen shield or contact lenses in the study eye 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 ripasudil 19. Has used netarsudil or eye drops and ointments containing ≥2% sodium chloride within 14 days prior to Visit 1 20. Has participated in any investigational drug or device clinical studies within 30 days of Visit 1 or is planning to participate in any investigational drug or device clinical studies during the study period 21. Has a positive urine test result for drugs of abuse (opiates, methadone, cocaine, amphetamines, barbiturates, or benzodiazepines) or alcohol at screening; however, drugs prescribed to treat current medical conditions are allowed 22. Is a member or a family member of the professional or ancillary personnel working at the study site or the Sponsor involved in the study 23. Has a concomitant medical or psychological condition that could interfere with study participation or is otherwise not suitable for entry into the study in the opinion of the Investigator 24. Is using any prohibited prescription or over-the-counter (OTC) medications or devices and is unwilling or unable to discontinue these medications or devices for the required time period before entry into the study 25. Is committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. 26. Has any ocular disease that may affect visual acuity in the study eye, such as glaucoma that has progressed to the central visual field, age-related macular degeneration, diabetic macular edema, amblyopia, etc

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to ≥40 ETDRS letter improvement in BCVA during the first 12 weeks after descemetorhexis.

Secondary endpoints 1

1. Key secondary endpoints: • 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 achievement of no corneal edema in both areas (epithelial, stromal) during the first 12 weeks after descemetorhexis. • Time to exceed pre-DSO ETDRS letter score in BCVA during the first 12 weeks after descemetorhexis.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kowa Research Institute Inc.

Sponsor organisation

Kowa Research Institute Inc.

Address

430 Davis Drive Suite 200

City

Morrisville

Postcode

27560-6802

Country

United States

Scientific contact point

Organisation

Kowa Research Institute Inc.

Contact name

Kelsey Behrens

Public contact point

Organisation

Kowa Research Institute Inc.

Contact name

Kelsey Behrens

Third parties 8

Locations

3 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications