K-321 Eye Drops for Fuchs' Dystrophy

Recruiting at 54 trial locations

Overseen By Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Kowa Research Institute, Inc.

Disqualifiers: Pregnancy, Recent cataract surgery, 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

107 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The protocol does not specify whether you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the idea that K-321 Eye Drops for Fuchs' Dystrophy is an effective drug?

The available research shows that K-321 Eye Drops, also known as Ripasudil, are primarily used for treating glaucoma and ocular hypertension by lowering eye pressure. There is no specific data provided about its effectiveness for Fuchs' Dystrophy. However, studies indicate that Ripasudil can help with corneal endothelial injuries, which might be relevant to Fuchs' Dystrophy. The research also highlights that Ripasudil can improve fluid drainage in the eye, which is beneficial for conditions involving eye pressure. While these findings are promising, they do not directly support the effectiveness of K-321 Eye Drops for Fuchs' Dystrophy specifically. ^{1 2 3 4 5}

What data supports the effectiveness of the drug K-321 Eye Drops for Fuchs' Dystrophy?

Ripasudil, a component of K-321 Eye Drops, is effective in lowering intraocular pressure in glaucoma and ocular hypertension by improving fluid outflow in the eye, which may suggest potential benefits for eye conditions like Fuchs' Dystrophy. ^{1 2 3 4 5}

What safety data is available for K-321 eye drops for Fuchs' Dystrophy?

The provided research articles do not contain any safety data related to K-321 eye drops or its other names such as Ripasudil, Glanatec, K-115, or Ripasudil hydrochloride hydrate. The studies focus on other eye treatments and conditions, such as dry eye syndrome and uveitis, and do not mention K-321 or its related compounds. ^{6 7 8 9 10}

Is the drug Ripasudil a promising treatment for Fuchs' Dystrophy?

Ripasudil is a promising drug because it has been shown to effectively lower eye pressure, which is important for treating eye conditions like glaucoma. It works by helping fluid flow out of the eye more easily, and it has been approved for use in Japan. This suggests it could be beneficial for other eye conditions, like Fuchs' Dystrophy, by potentially improving eye health and function. ^{1 2 3 4 11}

How is the drug Ripasudil unique for treating Fuchs' Dystrophy?

Ripasudil is unique because it is a Rho-associated kinase inhibitor that may help with corneal endothelial cell function, which is relevant for Fuchs' Dystrophy, a condition affecting the cornea. Unlike other treatments, it has been shown to influence corneal endothelial cell morphology and wound healing, potentially offering a novel approach for managing this condition. ^{1 2 3 4 11}

What is the purpose of this trial?

This trial is testing K-321 to help people with an eye condition called FECD recover after a corneal procedure. The treatment aims to support the growth and repair of eye cells.

Research Team

Shona Pendse, MD, MMSc

Principal Investigator

Kowa Pharma Development Co.

Eligibility Criteria

This trial is for adults over 18 with Fuchs Endothelial Corneal Dystrophy (FECD) who have not had cataract surgery in the last 90 days. Women must not be pregnant, breastfeeding, or of childbearing potential unless using effective birth control or are surgically sterile/post-menopausal.

Inclusion Criteria

I have been diagnosed with Fuchs' Endothelial Corneal Dystrophy.

Meets all other inclusion criteria outlined in clinical study protocol

Exclusion Criteria

I am a woman who can have children and am using effective birth control.

I had cataract surgery on one eye within the last 90 days.

Meet any other exclusion criteria outlined in clinical study protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive K-321 or placebo eye drops four times daily for 12 weeks

12 weeks

Dose Taper

Participants undergo a gradual dose taper of the eye drops

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

38 weeks

Treatment Details

Interventions

• Placebo
• Ripasudil

Trial Overview The study tests K-321 eye drops' safety and effectiveness on patients with FECD after a procedure called descemetorhexis. Participants will either receive Ripasudil (K-321) or a placebo to compare outcomes.

Participant Groups

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+

Findings from Research

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 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, 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 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, 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]

The new-generation ophthalmic solution (CXHAL) containing cross-linked hyaluronic acid and other components was found to be safe and effective for treating moderate to severe dry eye disease, with no reported adverse events in a study of 41 subjects over 2 months.

CXHAL demonstrated statistically significant improvements in tear break-up time and symptom assessment compared to the standard treatment (TRS), indicating its superior efficacy in enhancing ocular surface health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy, Tolerability and Safety of a New Multiple-Action Eyedrop in Subjects with Moderate to Severe Dry Eye. Roszkowska, AM., Inferrera, L., Spinella, R., et al.[2023]

In a study involving 438 patients with moderate to severe dry eye syndrome, 0.15% hyaluronic acid (HA) eyedrops were found to be as effective as 0.05% cyclosporine A (CsA) in improving corneal staining scores and other measures of eye health over 12 weeks.

The 0.15% HA treatment showed better tolerability and a lower incidence of adverse drug reactions compared to CsA, suggesting it may be a safer option for patients with dry eye syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized multicenter evaluation of the efficacy of 0.15% hyaluronic acid versus 0.05% cyclosporine A in dry eye syndrome. Lee, JE., Kim, S., Lee, HK., et al.[2023]

A new formulation of tacrolimus eye drops, developed using hydroxypropyl-β-cyclodextrin (HPβCD), shows promising stability and safety for treating uveitis, an inflammatory eye condition, with formulations remaining stable for at least 3 months in refrigeration.

The new eye drops demonstrated superior mucoadhesive properties and longer ocular permanence compared to existing reference formulations, suggesting they could be a more effective treatment option for patients with corticosteroid-refractory eye disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop. García-Otero, X., Díaz-Tomé, V., Varela-Fernández, R., et al.[2021]

In a study of 75 children aged 4-11, the combination of cyclopentolate and phenylephrine (CP) produced similar cycloplegic effects to the combination of tropicamide, cyclopentolate, and phenylephrine (TCP), indicating that omitting tropicamide does not significantly affect the ability to relax the eye for examination.

While TCP resulted in slightly larger pupil sizes and reduced light responsiveness in children with dark irides, the differences were minor and all pupils achieved adequate dilation for eye examinations, suggesting that CP alone is a viable alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tropicamide has limited clinical effect on cycloplegia and mydriasis when combined with cyclopentolate and phenylephrine. Sherman, AE., Shaw, MM., Ralay-Ranaivo, H., et al.[2020]

In a study involving 84 patients with severe dry eye disease, substituting their regular artificial tears with 0.15% high molecular weight hyaluronan (HMWHA) eye drops led to a significant improvement in symptoms, as measured by the Ocular Surface Disease Index (OSDI), with an average improvement of 13.5 points after 8 weeks.

The use of HMWHA eye drops also resulted in a slight improvement in best corrected visual acuity (BCVA), indicating that these drops can enhance patient comfort and vision without negatively affecting other dry eye signs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial. van Setten, GB., Baudouin, C., Horwath-Winter, J., et al.[2020]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Ripasudil: first global approval. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) Transiently Alters the Morphology of Corneal Endothelial Cells. [2015]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of the Rho-Associated Kinase Inhibitor Eye Drop (Ripasudil) on Corneal Endothelial Wound Healing. [2016]

5. China pubmed.ncbi.nlm.nih.gov

Effects of 0.4% ripasudil hydrochloride hydrate on morphological changes in rabbit eyes. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Efficacy, Tolerability and Safety of a New Multiple-Action Eyedrop in Subjects with Moderate to Severe Dry Eye. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A randomized multicenter evaluation of the efficacy of 0.15% hyaluronic acid versus 0.05% cyclosporine A in dry eye syndrome. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Tropicamide has limited clinical effect on cycloplegia and mydriasis when combined with cyclopentolate and phenylephrine. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

The HYLAN M Study: Efficacy of 0.15% High Molecular Weight Hyaluronan Fluid in the Treatment of Severe Dry Eye Disease in a Multicenter Randomized Trial. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ripasudil, a Rho-associated kinase inhibitor, in eyes with uveitic glaucoma. [2018]