Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus

A Study Evaluating the Safety and Efficacy of the KXL System With vibeX Rapid (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in Eyes Having Keratoconus and Post LASIK Ectasia

The objectives of this study are to evaluate the safety of and efficacy of the KXL system with vibeX Rapid (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in eyes having:

1. Keratoconus (KC) ,
2. Post LASIK ectasia (PLEc)

Study Overview

• Status: Unknown
• Conditions: Keratoconus; Post LASIK Keratectasia
• Intervention / Treatment: Radiation: 0.1% Riboflavin ophthalmic solution (KXL System With vibeX Rapid); Procedure: simultaneous KXL and topography-guided transepithelial photorefractive keratectomy(PRK)

Detailed Description

KC and Plec eyes Group 1 (non-randomised controlled)

Eyes will be assigned into 2 groups:

• Treatment eyes group with KXL
• Control eyes group (fellow eye) The Treatment eyes will be cross linked with the KXL system and the vibeX Rapid Riboflavin, while the control eyes will not receive any treatment.

The safety and efficacy endpoints will be evaluated and compared between the Treatment eye group and the Control eye group.

After 6 months of follow up the KC and PLEc subjects will be offered to treat the control eyes if indicated.

Group 2 (non-randomised controlled combined treatment)

Eyes will be assigned into 2 groups:

• Treatment group with simultaneous KXL and topography-guided transepithelial photorefractive keratectomy(PRK)
• Control eyes group (fellow eye) The Treatment eyes will undergo simultaneous topography-guided PRK and be cross linked with the KXL system and the vibeX Rapid Riboflavin, while the control eyes will not receive any treatment.

The safety and efficacy endpoints will be evaluated and compared between the Treatment eye group and the Control eye group.

After 6 months of follow up the KC and PLEc subjects will be offered to treat the control eyes if indicated.

The concentrations of Riboflavin Ophthalmic Solution will be tested - 0.1% Riboflavin ophthalmic solution

KC Eyes will be irradiated at 30mW/cm2 for 4 minutes continuous treatment or 8 minutes pulse treatment: 1 second on 1 second off.

PLEc Eyes will be irradiated at 30mW/cm2 for 4 minutes continuous treatment or 8 minutes pulse treatment: 1 second on 1 second off..

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chuan Teck Ang, Diploma; Email: ang.chuan.teck@seri.com.sg
• Study Contact Backup: Name: Mohamed Farook Kothubutheen, BSc (Hons); Email: farook@snec.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 168751
    • Recruiting
    • Singapore National Eye Centre
    • Contact: Chuan Teck Ang, Diploma; Email: ang.chuan.teck@seri.com.sg
    • Contact: Mohamed Farook Kothubutheen, BSc (Hons); Email: farook@snec.com.sg
    • Principal Investigator: Li Lim, MBBS,FRCS
    • Sub-Investigator: Tiang Hwee, Donald Tan, MBBS,FRCS
    • Sub-Investigator: Jodhbir S Mehta, MBBS,FRCS
    • Sub-Investigator: Mei Lan, Cordelia Chan, MBBS,FRCS
    • Sub-Investigator: Seng Ei Ti, MBBS,FRCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age Limit for for keratoconus and Plec:18 years
2. Sign the informed consent.
3. Willingness and ability to follow all instructions and comply with schedule for follow-up visits;

4. Contact Lens Wearers Only:

   Minimum of 3 days

5. For KC subjects:

   1. Axial topography consistent with keratoconus(Pentacam )
   2. Presence of central or inferior steepening on the Pentacam map;
   3. Steepest keratometry (Kmax) value ≥ 47.00 D;
   4. May have corneal scarring up to and including CLEK grade 4.0 (any scarring up to a dense/opaque stromal scar consistent with KC)
   5. Keratoconus progressing over time ( evidenced by topography changes, visual acuity or refractive changes)

6. For PLEc subjects:

   1. Having a diagnosis of corneal ectasia after corneal refractive surgery (e.g., LASIK, PRK, epi-LASIK,LASEK,)
   2. Presence of central or inferior steepening on the Pentacam map.
   3. Axial topography consistent with corneal ectasia

Exclusion Criteria:

1. Contraindications, sensitivity or known allergy to the use of the test article(s) or their components;
2. If female, be pregnant, nursing or planning a pregnancy or have a positive urine pregnancy test at Visit 2 prior to randomization or during the course of the study;
3. For KC and PLEc subjects, corneal pachymetry that is < 400microns prior to epithelial debridement at the thinnest point measured by Pentacam in the eye to be treated;
4. A history of chemical injury or delayed epithelial healing in the eye(s) to be treated;
5. Patients with nystagmus or any other condition that would prevent a steady gaze during the treatment or other diagnostic tests;
6. Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing;
7. Taking Vitamin C (ascorbic acid) supplements within 1 week of the cross-linking treatment,retinoic acid within 6 months of treatment

8. Previous ocular condition (other than refractive error) in the eye to be treated that may predispose the eye for future complications. For example:

   8.1. History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, corneal dystrophy, etc.); 8.2. Clinically significant corneal scarring in the cross-linking treatment zone or in the investigator's opinion, will interfere with the cross-linking procedure;

9. For KC subjects 9.1. Eyes which are aphakic; 9.2. Eyes that have the maximum corneal curvature (Kmax), as identified and measured by Pentacam, outside of the central 5mm zone; Note: In addition, the Investigator may exclude or discontinue any subject for any sound medical reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: KXL treatment only	Radiation: 0.1% Riboflavin ophthalmic solution (KXL System With vibeX Rapid); KC Eyes will be irradiated at 30mW/cm2 for 4 minutes continuous or 8 minutes pulse treatment: 1 second on 1 second off. PLEc Eyes will be irradiated at 30mW/cm2 for 4 minutes continuous or 8 minutes pulse treatment: 1 second on 1 second off.
Active Comparator: KXL and topography-guided PRK; simultaneous KXL and topography-guided transepithelial photorefractive keratectomy(PRK)	Radiation: 0.1% Riboflavin ophthalmic solution (KXL System With vibeX Rapid); KC Eyes will be irradiated at 30mW/cm2 for 4 minutes continuous or 8 minutes pulse treatment: 1 second on 1 second off. PLEc Eyes will be irradiated at 30mW/cm2 for 4 minutes continuous or 8 minutes pulse treatment: 1 second on 1 second off.; Procedure: simultaneous KXL and topography-guided transepithelial photorefractive keratectomy(PRK); The (Partial, Spherically Corrected) Topography-guided Transepithelial PRK Technique. Is performed with WaveLight® EX 500 excimer laser (Alcon Laboratories Inc, Ft Worth, Texas) customized platform. This software utilizes topographic data from the linked topography device (Topolyzer; Wave- Light GmbH, Erlangen, Germany). The image of the planned surgery is generated by the laser software. The topography-guided PRK is used to normalize the cornea by reducing irregular astigmatism while treating part of the refractive error. The maximum ablation depth of stromal ablation is set at 50um. A 6.5-mm, 50-μm phototherapeutic keratectomy (PTK) was performed to remove the corneal epithelium. Partial topography- guided PRK laser treatment was applied. A cellulose sponge soaked in mitomycin C (MMC) 0.02% solution was applied over the ablated tissue for 20 seconds followed by irrigation with 10 mL of chilled balanced salt solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Measure: Change in Best Corrected Visual Acuity (LogMAR) at 6 months and 1 year	A study evaluating the safety and efficacy of the KXL system with vibeX Rapid (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in eyes having Keratoconus and post LASIK ectasia	6 months and 1 year
Safety measure: change in endothelial cell counts(cells/mm2) at 6 months and 1 year	A study evaluating the safety and efficacy of the KXL system with vibeX Rapid (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-linking in eyes having keratoconus and LASIK ectasia	6 months and 1 year
Efficacy measure: Change in Corneal keratometry measurement, Kmax(D) at 6 months and 1 year	A study evaluating the safety and efficacy of the KXL system with vibeX Rapid (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-linking in eyes having keratoconus and LASIK ectasia	6 months and 1 year

Collaborators and Investigators

• Sponsor: Singapore Eye Research Institute
• Investigators: Principal Investigator: Li Lim, MBBS, FRCS, Singapore National Eye Centre, Singapore Eye Research Institute

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): December 1, 2015
• Study Completion (Anticipated): June 1, 2016

Study Registration Dates

• First Submitted: September 29, 2014
• First Submitted That Met QC Criteria: December 22, 2015
• First Posted (Estimate): December 23, 2015

Study Record Updates

• Last Update Posted (Estimate): December 23, 2015
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: treatment; Keraroconus; keratectasia
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Pharmaceutical Solutions; Ophthalmic Solutions; Riboflavin
• Other Study ID Numbers: R963/72/2012