Corneal Cross-Linking for Keratoconus

Recruiting at 3 trial locations

Overseen By Marco Armijo

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Glaukos Corporation

Disqualifiers: Allergy, Abnormal topography, Ocular condition

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for keratoconus, a condition where the cornea becomes thin and cone-shaped. The researchers aim to determine if a riboflavin (vitamin B2) solution combined with UV-A light can safely and effectively strengthen the cornea. The trial includes several treatments with different energy levels—NXL Energy 1, NXL Energy 2, and NXL Energy 3—and a placebo group receiving no actual treatment. Individuals diagnosed with keratoconus who can keep their eyes steady during tests might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that corneal cross-linking is generally safe for treating keratoconus. This treatment uses a special vitamin B2 solution (riboflavin) and UV-A light and is usually well-tolerated. Long-term studies indicate it is safe, though rare serious complications can occur. The treatment aims to stop keratoconus, a condition affecting the eye's cornea, from worsening, and data supports its effectiveness in most cases.

The investigational treatments in this trial, NXL Energy 1, 2, and 3, are variations of this method. Previous studies have demonstrated that this approach is safe and can help avoid more serious procedures like a corneal transplant. While these treatments are in the early stages of testing, meaning they are still being closely studied for safety and effectiveness, earlier research on similar treatments provides encouraging safety evidence. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for keratoconus work by reshaping the cornea using contact lenses or surgical procedures. But the investigational treatments in this trial are unique because they enhance corneal strength through a process called corneal cross-linking, which uses riboflavin (a type of vitamin B2) combined with UV-A light exposure. These NXL Energy treatments differ by delivering varying energy levels during the cross-linking process, potentially offering more tailored and effective options for individual patients. Researchers are excited because this approach could improve corneal stability and reduce the progression of keratoconus, offering a non-invasive alternative to more traditional methods.

What evidence suggests that this trial's treatments could be effective for keratoconus?

Research has shown that corneal cross-linking (CXL) is a safe and effective treatment for keratoconus, a condition where the cornea becomes thin and cone-shaped. Studies indicate that CXL can help prevent the condition from worsening. For example, one study found that CXL reduced the steepness of the cornea by an average of 1.9 diopters, indicating improvement. Additionally, long-term results are encouraging, with many patients maintaining stable vision for years after treatment. Most patients in these studies did not experience further progression of their condition after undergoing CXL, making it a reliable option for stabilizing keratoconus. In this trial, participants will receive different versions of the CXL treatment or a sham treatment to evaluate the effectiveness of each approach. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with keratoconus, a condition that affects the shape of the cornea. Participants must be able to keep their gaze stable and give written consent. It's not open to those with other diseases affecting eye topography, prior eye conditions that could complicate results, or allergies to components used in the treatments.

Inclusion Criteria

Provide written informed consent

I have been diagnosed with keratoconus.

I can keep my eyes fixed on one point without moving.

Exclusion Criteria

Known allergy or sensitivity to the test articles or components

I have an eye condition that is not keratoconus.

I have an eye condition that could lead to future problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Riboflavin Ophthalmic Solution and UV-A Irradiation or a sham solution as part of the corneal cross-linking procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in visual acuity and corneal topography

12 months

Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• NXL Energy 1
• NXL Energy 2
• NXL Energy 3
• Sham Treatment

Trial Overview The study tests three different energy levels (NXL Energy 1, NXL Energy 2, NXL Energy 3) of corneal cross-linking against a sham treatment to see which is safest and most effective at stabilizing the cornea in keratoconus patients.

How Is the Trial Designed?

Group I: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 1 / Cohort 1 Experimental Treatment 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 3

Group II: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 3 / Cohort 2A Active Control 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 1

Group III: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 4 / Cohort 2A Active Control 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 2

Group IV: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 5 / Cohort 2A Active Control 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 3

Group V: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 3 / Cohort 2B Active Control 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 1

Group VI: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 4 / Cohort 2B Active Control 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 2

Group VII: Riboflavin Ophthalmic Solution and UV-A Irradiation Group 5 / Cohort 2B Active Control 1 Intervention

Riboflavin Solution + Exposure to NXL system to achieve total energy level 3

Group VIII: Placebo Group 2 / Cohort 2B Placebo Group 1 Intervention

Sham Solution with no exposure to NXL System

NXL Energy 1 is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Corneal Cross-linking for:

• Keratoconus
• Ectasia

Approved in United States as Corneal Cross-linking for:

• Keratoconus
• Progressive Ectasia

Approved in Canada as Corneal Cross-linking for:

• Keratoconus
• Ectasia

Who Is Running the Clinical Trial?

Glaukos Corporation

Lead Sponsor

Trials

69

Recruited

9,500+

Thomas Burns

Glaukos Corporation

Chief Executive Officer since 2002

B.A. from Yale University

Dr. Tomas Navratil

Glaukos Corporation

Chief Medical Officer since 2022

MD from Harvard Medical School

Published Research Related to This Trial

In a study of 27 eyes from 24 patients with progressive keratoconus, customized corneal crosslinking (CXL) using a transepithelial approach and supplemental oxygen led to significant improvements in corrected distance visual acuity (CDVA) and corneal curvature after 6 months.

The procedure resulted in a flattening of steep keratometry by an average of -1.9 diopters and a reduction in corneal aberrations, all without significant adverse events, indicating its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Customized corneal crosslinking for treatment of progressive keratoconus: Clinical and OCT outcomes using a transepithelial approach with supplemental oxygen. Mazzotta, C., Sgheri, A., Bagaglia, SA., et al.[2021]

A combined treatment of topography-guided photorefractive keratectomy (PRK) with mitomycin-C and corneal collagen cross-linking (CXL) significantly improved best corrected visual acuity in patients with mild to moderate keratoconus over a 2-year follow-up, with a notable improvement from 0.15 to 0.08 logMAR.

The procedure also effectively reduced keratometry measurements, indicating a flattening of the cornea, which is crucial for managing keratoconus, with significant reductions in both steepest and flattest meridian keratometry values.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined photorefractive keratectomy and corneal collagen cross-linking for treatment of keratoconus: a 2-year follow-up study. De Rosa, G., Rossi, S., Santamaria, C., et al.[2022]

Collagen cross-linking (CXL) is a safe and effective treatment for halting the progression of advanced keratoconus, with 27 out of 28 eyes showing no further progression after the procedure.

Despite starting with a high maximum keratometry (maxK) of 61.2 D, CXL led to a significant reduction in maxK to 59.5 D, indicating that CXL can be beneficial even in cases previously thought to have a higher risk of treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Collagen cross-linking for advanced progressive keratoconus. Ivarsen, A., Hjortdal, J.[2022]

Corneal cross-linking (CXL) has been established as a safe and effective treatment for keratoconus and corneal ectasias, supported by numerous laboratory and clinical studies.

Recent research is paving the way for advancements in CXL techniques, including accelerated methods and epithelium-sparing protocols, which may enhance treatment outcomes and broaden the applications of CXL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and future applications of corneal cross-linking. Khandelwal, SS., Randleman, JB.[2018]

Standard corneal collagen crosslinking (epithelium-off CXL) is more effective than transepithelial CXL in reducing maximum keratometry in patients with keratoconus, based on a study of 244 eyes over at least 12 months.

Transepithelial CXL resulted in better improvements in corrected distant visual acuity (CDVA) compared to standard CXL, while both methods showed similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of transepithelial corneal collagen crosslinking surgery versus standard corneal collagen crosslinking surgery for keratoconus: a meta-analysis of randomized controlled trials. Li, W., Wang, B.[2022]

Accelerated corneal cross-linking (CXL) showed significant improvements in keratometric values in pediatric patients with keratoconus, indicating its efficacy in stabilizing the condition, although it did not lead to significant changes in visual acuity.

Both accelerated and conventional CXL were effective in managing keratoconus, with the accelerated method offering a shorter treatment time, making it a viable alternative for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Conventional Versus Accelerated Corneal Cross-linking in Pediatric Keratoconus: Two-Year Outcomes. Turhan, SA., Yargi, B., Toker, E.[2021]

In a case series of four keratoconus patients treated with corneal collagen cross-linking (CXL), severe complications occurred within the first month, including bacterial infections and an autoimmune response, leading to permanent corneal scarring in some cases.

While severe complications after CXL are rare, they often arise from indirect factors during the healing process, such as patient behavior and the use of bandage contact lenses, highlighting the need for improved techniques and careful postoperative management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Complications after Corneal Collagen Cross-Linking (CXL). Blaser, F., Zweifel, S., Wiest, MRJ., et al.[2023]

Corneal cross-linking (CXL) has proven to be an effective and safe treatment for halting the progression of keratoconus and other corneal ectasias, with its use now extending to patients at risk of progression, particularly younger individuals.

The outcomes of CXL can vary, and different treatment protocols exist, highlighting the importance of careful patient selection and consideration of specific cases, such as those with thin corneas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection for corneal collagen cross-linking: an updated review. Galvis, V., Tello, A., Ortiz, AI., et al.[2020]

In a study of 239 eyes from 171 patients with progressive keratoconus, the CXL-plus-PTK procedure showed superior effectiveness compared to the standard Accelerated CXL, particularly in reducing maximum keratometry (Kmax).

The Iontophoresis CXL procedure also demonstrated better outcomes in terms of minimum corneal thickness (C value) compared to the Accelerated CXL group, indicating that different CXL modalities can have varying impacts on corneal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent-effect comparison of five crosslinking procedures for Progressive Keratoconus based on Keratometry and the ABCD Grading System using Generalized Estimating Equations (GEE). Liu, Y., Shen, D., Wang, HY., et al.[2023]

In a study of 96 patients with keratoconus, 39.6% experienced disease progression during an average waiting time of 153 days before receiving corneal cross-linking (CXL) treatment.

Specific preoperative tomographic parameters, such as the index of surface variance and keratoconus index, were significantly different between eyes that progressed and those that remained stable, suggesting these factors could help identify patients at higher risk for progression while awaiting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Clinical Study of Keratoconus Progression in Patients Awaiting Corneal Cross-linking. Goh, YW., Gokul, A., Yadegarfar, ME., et al.[2021]

Corneal cross-linking (CXL) significantly improved best-corrected visual acuity (BCVA) in patients with progressive keratoconus, with an average BCVA of 0.8 six months post-procedure compared to lower scores before treatment.

CXL also led to a reduction in spherical equivalent refraction, cylinder, and maximum keratometry (max K), indicating enhanced corneal stability and potential refractive benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The results of corneal cross-linking in the treatment of keratoconus. Kasumovic, SS., Pavljasevic, S., Dacic-Lepara, S., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10302271/

Safety and Efficacy of Corneal Cross-Linking in Patients ... CXL is a safe and effective treatment for avoiding keratoconus progression. Long-term data are encouraging, supporting a high safety profile for this procedure.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11953132/

Pulsed corneal crosslinking in the treatment of Keratoconus Overall, P-CXL is effective in improving visual acuity and keratometry outcomes in keratoconus. The meta-analysis did not show a statistically significant ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04532788

Efficacy of Customized Corneal Cross-linking vs. Standard ... Recently published studies provide clinical evidence that similar clinical outcomes (amount of corneal flattening) can be achieved when only the cone is treated ...

4. eyewiki.org eyewiki.org/Corneal_Cross-Linking

Corneal Cross-Linking Corneal collagen cross-linking (CXL) is a minimally invasive procedure used to prevent progression of corneal ectasias such as keratoconus and post-LASIK ...

5. withpower.com withpower.com/trial/phase-2-progressive-keratoconus-2-2022-fed6a

Corneal Cross-Linking for Keratoconus This trial is testing a treatment that uses light and vitamins to strengthen the cornea in people with keratoconus, a condition that makes the cornea thin ...

6. ctv.veeva.com ctv.veeva.com/study/safety-and-efficacy-of-corneal-cross-linking-in-subjects-with-keratoconus

Safety and Efficacy of Corneal Cross-linking in Subjects With ... This is aa dose ranging, multi-center, sham-controlled study to evaluate the safety and efficacy of epithelium-on corneal collagen cross-linking.

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05314738/safety-and-efficacy-of-corneal-cross-linking-in-subjects-with-keratoconus

Safety and Efficacy of Corneal Cross-linking in Subjects ... Clinical Trial to Evaluate the Safety and Efficacy of Corneal Cross-linking in Subjects with Keratoconus ... Primary Treatment: NXL Energy 1.

8. vision-institute.com vision-institute.com/wp-content/uploads/United-States-Multicenter-Clinical-Trial-of-Corneal-Collagen-Crosslinking-for-Keratoconus-Treatment.pdf

United States Multicenter Clinical Trial of Corneal Collagen ... Purpose: To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus.