K-321 Eye Drops for Fuchs' Dystrophy

No longer recruiting at 58 trial locations

Overseen By Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kowa Research Institute, Inc.

Disqualifiers: Pregnancy, Breastfeeding, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an eye drop called K-321 (Ripasudil) to determine its effectiveness for people with Fuchs' Dystrophy, a condition affecting the cornea that can lead to vision problems. The study will assess the safety and effectiveness of the eye drop after patients undergo cataract surgery and descemetorhexis, a procedure that removes a layer of the cornea. Participants will receive either the actual eye drop or a placebo for 12 weeks, followed by a tapering phase and long-term follow-up. Individuals diagnosed with Fuchs' Dystrophy and scheduled for these surgeries may be suitable for the trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Ripasudil eye drops, also known as K-321, have been safe in earlier studies. These studies included patients who used Ripasudil after eye surgeries similar to those in this trial. The treatment was generally well-tolerated, with most side effects being mild and temporary, such as eye irritation or redness.

One study found that people using Ripasudil after certain eye surgeries did not experience serious side effects. This suggests that Ripasudil is generally safe for eye conditions like Fuchs' dystrophy. However, as with any treatment, individual reactions can differ, so discussing any concerns with the medical team involved in the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Fuchs' Dystrophy?

Unlike the standard treatments for Fuchs' Dystrophy, which often involve corneal transplants or endothelial keratoplasty, K-321 eye drops utilize the active ingredient ripasudil. This treatment is unique because ripasudil is a Rho kinase inhibitor, a novel mechanism that targets the cellular dysfunction in the cornea, potentially promoting healing and reducing the need for surgery. Researchers are excited about K-321 because it offers a non-surgical option that could preserve vision and improve quality of life for patients with this condition.

What evidence suggests that K-321 eye drops might be an effective treatment for Fuchs' dystrophy?

Research shows that Ripasudil, also known as K-321, may help treat Fuchs' endothelial corneal dystrophy (FECD). In this trial, participants will receive either Ripasudil or a placebo. Studies suggest that Ripasudil, a type of medication called a ROCK inhibitor, can protect the cornea by reducing the loss of important cells in the eye after surgery. These cells are crucial for keeping the cornea clear and ensuring good vision. Early results indicate that Ripasudil can aid in corneal healing and improve recovery after certain eye surgeries, like descemetorhexis. Patients using ROCK inhibitors, such as Ripasudil, have shown better corneal health in similar conditions. Overall, researchers are carefully studying this treatment for its potential benefits for people with FECD. ^{2 3 5 6 7}

Who Is on the Research Team?

Shona Pendse, MD, MMSc

Principal Investigator

Kowa Pharma Development Co.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Fuchs Endothelial Corneal Dystrophy (FECD) who are undergoing cataract surgery and descemetorhexis. Participants must meet all other criteria specified in the study protocol.

Inclusion Criteria

Meet all other inclusion criteria outlined in the Clinical Study Protocol.

I have been diagnosed with Fuchs' dystrophy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive K-321 or placebo ophthalmic solution four times daily for 12 weeks

12 weeks

Dose Taper

Participants undergo a two-week gradual dose taper phase

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Ripasudil

Trial Overview The trial is testing K-321 eye drops to see if they're safe and effective when used after cataract surgery and descemetorhexis in patients with FECD, compared to a placebo.

How Is the Trial Designed?

Group I: K-321 Experimental Treatment 1 Intervention

K-321 ophthalmic solution four times daily (QID) for 12 weeks followed by a two-week gradual dose taper phase and 38-week follow-up phase

Group II: Placebo Placebo Group 1 Intervention

Placebo ophthalmic solution QID for 12 weeks followed by a two-week gradual dose taper phase and 38-week follow-up phase

Ripasudil is already approved in Japan for the following indications:

Approved in Japan as Glanatec for:

• Glaucoma
• Ocular hypertension

Who Is Running the Clinical Trial?

Kowa Research Institute, Inc.

Lead Sponsor

Trials

46

Recruited

16,400+

Published Research Related to This Trial

Ripasudil hydrochloride hydrate, when used continuously in rabbit eyes, leads to structural changes such as increased intercellular space in the trabecular meshwork and ciliary body, which may enhance intraocular pressure reduction.

The treatment appears to improve both conventional and unconventional outflow pathways without causing serious side effects, indicating its potential efficacy and safety for managing intraocular pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 0.4% ripasudil hydrochloride hydrate on morphological changes in rabbit eyes. Limratchatamorn, B., Asakawa, K., Mashimo, K., et al.[2020]

Ripasudil eye drops significantly enhanced the healing of corneal endothelial cells, as shown by increased cell proliferation and regeneration in both cultured human cells and a rabbit model of corneal injury.

In the rabbit model, 91.5% of corneal endothelial cells treated with ripasudil were actively proliferating, leading to improved transparency in the corneas, indicating its potential as a treatment for corneal endothelial damage following eye surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) on Corneal Endothelial Wound Healing. Okumura, N., Okazaki, Y., Inoue, R., et al.[2016]

Ripasudil hydrochloride hydrate is an effective treatment for lowering intraocular pressure (IOP) in various types of glaucoma, including primary open-angle and angle-closure glaucoma, and can be used in different treatment scenarios such as monotherapy or combination therapy.

The most common side effect is mild conjunctival hyperemia, while serious systemic adverse reactions are rare; however, patient selection is crucial, as the effectiveness of ripasudil may be reduced in patients with irreversible damage to the trabecular meshwork.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ripasudil Hydrochloride Hydrate in the Treatment of Glaucoma: Safety, Efficacy, and Patient Selection. Kusuhara, S., Nakamura, M.[2020]

Ripasudil hydrochloride hydrate is an effective treatment for glaucoma and ocular hypertension, working by reducing intraocular pressure through its action on the trabecular meshwork to enhance fluid outflow.

The eye drop solution has been approved in Japan for use when other treatments are ineffective, and it may provide additional benefits when combined with other glaucoma medications, such as prostaglandin analogues and β blockers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ripasudil: first global approval. Garnock-Jones, KP.[2022]

Ripasudil, a ROCK inhibitor approved for glaucoma treatment, causes transient morphological changes in the corneal endothelium, resembling guttae, without disrupting corneal function or causing cell death.

The study found no severe adverse effects from ripasudil, but physicians should recognize these guttae-like changes to prevent misdiagnosis of conditions like Fuchs endothelial corneal dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Transiently Alters the Morphology of Corneal Endothelial Cells. Okumura, N., Okazaki, Y., Inoue, R., et al.[2015]

Ripasudil hydrochloride hydrate, a Rho-associated kinase inhibitor, significantly reduced intraocular pressure (IOP) in patients with uveitic glaucoma, with median IOP decreasing from 23 mmHg at baseline to 16 mmHg at 1 month and 18 mmHg at 12 months.

The treatment was found to be safe, with only two mild adverse events reported, and it may be particularly effective for patients who respond well to the medication, showing a greater IOP reduction over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ripasudil, a Rho-associated kinase inhibitor, in eyes with uveitic glaucoma. Kusuhara, S., Katsuyama, A., Matsumiya, W., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03813056

Study Details | NCT03813056 | Ripasudil for Enhanced ... The goal of this study is to test the potential benefits of Ripasudil therapy administered after Descemet Membrane Endothelial Keratoplasty (DMEK) surgery. We ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8423139/

A Close Look at the Clinical Efficacy of Rho-Associated ... ROCK-inhibitor eye drops may eventually be deemed a cutting-edge therapy for Fuchs endothelial corneal dystrophy patients with acute corneal endothelial defect.

3. sciencedirect.com sciencedirect.com/science/article/pii/S2451993623000476

Twelve-year outcome of Rho-associated protein kinase ... The purpose of this case report is to present the long-term outcome of the treatment by ROCK inhibitor eye drops and trans-corneal freezing of damaged CECs.

4. aao.org aao.org/education/editors-choice/rock-inhibitor-may-help-protect-cornea-post-phaco-

A ROCK Inhibitor May Help Protect the Cornea Post-Phaco ... The primary outcome was the percentage of central endothelial cell density (C-ECD) loss 3 months after cataract surgery. The authors also ...

5. cochranelibrary.com cochranelibrary.com/content?templateType=related&urlTitle=/central/doi/10.1002/central/CN-02169390&doi=10.1002/central/CN-02169390&p_p_id=scolariscontentdisplay_WAR_scolariscontentdisplay&_scolariscontentdisplay_WAR_scolariscontentdisplay_action=related-content&p_p_lifecycle=0&p_p_mode=view&type=central&contentLanguage=

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

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05795699?intr=GLANATEC&aggFilters=studyType:int&viewType=Table&rank=8

A Study to Evaluate the Safety and Efficacy of K-321 Eye Drops ... A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32740006/

Descemet Stripping Only Supplemented With Topical ... This trial of DSO supplemented with ripasudil included local and systemic safety analysis. We judge that this treatment option is emerging ...