A Phase 3 Study to Investigate the Safety and Efficacy of Ripasudil (K-321) in Subjects with Fuchs 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

9 Aug 2023 → 24 Oct 2025

Decision date (initial)

2023-07-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Kowa Research Institute, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To investigate the effect of K-321 on the time to improvement in BCVA by ETDRS letter score of ≥40 letters during the first 12 weeks after simultaneous cataract surgery and descemetorhexis in subjects with FECD.

Secondary objectives 3

1. 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 simultaneous cataract surgery and descemetorhexis.
2. 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 simultaneous cataract surgery and descemetorhexis.
3. To investigate the effect of K-321 on central corneal ECD at Week 12 after simultaneous cataract surgery and descemetorhexis.

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 8

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. Has a visually significant cataract in the study eye at Visit 1
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 assessments are performed.
7. 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.
8. Completion of cataract surgery and with the following conditions: a. Intraocular lens placement in the capsular bag without complications (eg, broken posterior capsule, need for anterior vitrectomy). b. Absence of Descemet membrane stripping or detachment outside the central zone (a small area of detachment or stripping may occur adjacent to the phaco wound and is acceptable if ≤0.5mm surface area). c. Confirmation via the operating microscope that the intraocular lens is in the correct location in the capsular bag. d. No AE noted by the surgeon during the surgery.

Exclusion criteria 26

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 simultaneous cataract surgery and descemetorhexis
3. Has had capsular rupture or infection in the study eye or any other complications or AEs during cataract surgery.
4. 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)
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 simultaneous cataract surgery and 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 simultaneous cataract surgery and 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
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 ripasudil
19. Has used netarsudil or eye drops and ointments containing ≥2% sodium chloride within 14 days prior to Visit 1
20. Has partecipated 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 simultaneous cataract surgery and descemetorhexis.

Secondary endpoints 3

1. Time to ≥20 ETDRS letter improvement during the first 12 weeks after simultaneous cataract surgery and descemetorhexis.
2. Time to achievement of ≥70 ETDRS letters during the first 12 weeks after simultaneous cataract surgery and descemetorhexis.
3. Central corneal ECD change from baseline at Week 12.

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 · 16 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 15 files

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

Application history

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