Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery

Multi-Center, Randomized, Controlled Evaluation of the Safety & Efficacy of the KXL System With VibeX (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery

The objectives of this study are to evaluate and compare the safety and efficacy of three treatment regimens for corneal collagen cross-linking performed with VibeX (riboflavin ophthalmic solution) and the KXL System in impeding the progression of, and/or reducing maximum corneal curvature.

Study Overview

• Status: Terminated
• Conditions: Keratoconus; Corneal Ectasia
• Intervention / Treatment: Device: KXL System (15 mW/cm2); Drug: riboflavin ophthalmic solution; Device: KXL System (30 mW/cm2); Device: KXL System (45 mW/cm2)

• Study Type: Interventional
• Enrollment (Actual): 1721
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Lilia Rivera
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • John Parker
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Barnet Dulaney Perkins Eye Center
  • California
    • Los Angeles, California, United States, 90067
      • Advanced Vision Care
    • Palo Alto, California, United States, 94303
      • Stanford University School of Medicine
    • Sacramento, California, United States, 95815
      • Grutzmacher, Lewis and Sierra
    • Sacramento, California, United States, 95816
      • Center for Sight
    • Sacramento, California, United States, 95821
      • Newman Lasik Centers
    • San Leandro, California, United States, 94578
      • Batra Vision Medical Group
    • Stockton, California, United States, 95207
      • Delta Eye Medical Group
    • Walnut Creek, California, United States, 94598
      • Kaiser Permanente - Kaiser Network Patients in Northern California Only
  • Colorado
    • Denver, Colorado, United States, 80210
      • Mile High Corneal Specialists, PC
  • Connecticut
    • Manchester, Connecticut, United States, 06040
      • Manchester Ophthalmology
    • Milford, Connecticut, United States, 06460
      • Eye Physicians and Surgeons, PC
  • Florida
    • Coral Gables, Florida, United States, 33134
      • TLC of Miami The Laser Center of Coral Gables
    • Delray Beach, Florida, United States, 33484
      • Delray Eye Associates, PA
    • Hallandale Beach, Florida, United States, 33009
      • Braverman Eye Center
    • Largo, Florida, United States, 33770
      • The Eye Institute of West Florida
    • Orlando, Florida, United States, 32803
      • Herschel Lasik
    • Tampa, Florida, United States, 33607
      • LCA-Vision Inc
  • Illinois
    • Belleville, Illinois, United States, 62226
      • Quantum Vision Centers
  • Iowa
    • Coralville, Iowa, United States, 52241
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Kansas LasikPlus, P.A.
    • Wichita, Kansas, United States, 67208
      • Grene Vision Group
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • LaskiPlus Vision Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Medical Center
  • Maine
    • Portland, Maine, United States, 04102
      • Eyecare Medical Group
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • GBMC Dept. of Opthalmology/Mid-Atlantic Cornea Consultants
    • Bowie, Maryland, United States, 20716
      • Solomon Eye Physicians and Surgeons
    • Chevy Chase, Maryland, United States, 20815
      • Eye Doctors of Washington
  • Massachusetts
    • Brookline, Massachusetts, United States, 02446
      • Boston Eye Group
    • Waltham, Massachusetts, United States, 02451
      • Ophthalmic Consultants of Boston
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49546
      • Verdier Eye Center P.L.C.
    • Southfield, Michigan, United States, 48034
      • Michigan Cornea Consultants
  • Minnesota
    • Bloomington, Minnesota, United States, 55420
      • Chu Vision Institute
  • Mississippi
    • Madison, Mississippi, United States, 39110
      • Eye Surgery and Laser Center
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Pepose Vision Institute/ Lifelong Vision Foundation
    • Saint Louis, Missouri, United States, 63131
      • Ophthamology Consultants LLC
  • Montana
    • Billings, Montana, United States, 59102
      • The Eye Clinic Surgicenter
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Eye Surgical Associates
    • Omaha, Nebraska, United States, 68144
      • Kugler Vision, PC
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Wellish Vision Institute
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Eye Group
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Eye Associates of New Mexico
  • New York
    • De Witt, New York, United States, 13214
      • CNY Eye Care
    • Great Neck, New York, United States, 11021
      • North Shore LIJ Health Systems
    • Pomona, New York, United States, 10970
      • Ramapo Ophthalmology Associates, LLP
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Carolina Vision Center
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Bagan Strinden Vision
  • Ohio
    • Westerville, Ohio, United States, 43082
      • Comprehensive Eye Care of Central Ohio
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Dean McGee Eye Institute
  • Oregon
    • Portland, Oregon, United States, 97210
      • Devers Eye Institute
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute/OHSU
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19004
      • Ophthalmic Partners of PA, P.C.
    • Harrisburg, Pennsylvania, United States, 17110
      • Schein Ernst Eye Associates
    • Philadelphia, Pennsylvania, United States, 19104
      • Scheie Eye Institute, University of Pennsylvania School of Medicine
    • Philadelphia, Pennsylvania, United States, 19107
      • Corneal Associates, Wills Eye Institute
    • Scranton, Pennsylvania, United States, 18503
      • Northeastern Eye Institute
    • Wilkes-Barre, Pennsylvania, United States, 18702
      • Bucci Laser Vision Institute
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
    • Rapid City, South Dakota, United States, 57701
      • Wright Vision Center
    • Sioux Falls, South Dakota, United States, 57108
      • Vance Thompson Vision
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Loden Vision Center
    • Nashville, Tennessee, United States, 37203
      • Wang Vision Institute
  • Texas
    • Austin, Texas, United States, 78746
      • Dell Laser Consultants
    • El Paso, Texas, United States, 79902
      • Buena Vista Eyecare
    • Grapevine, Texas, United States, 76051
      • Eye Consultants of Texas
    • Houston, Texas, United States, 77027
      • Berkeley Eye Center
    • Houston, Texas, United States, 77027
      • Slade and Baker Vision Center
    • San Antonio, Texas, United States, 78229
      • Focal Point Vision
  • Utah
    • Draper, Utah, United States, 84020
      • Hoopes Vision
    • Salt Lake City, Utah, United States, 84107
      • The Eye Institute of Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Dept. of Ophthalmology & Visual Sciences
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Silk Vision & Surgical Center
    • Norfolk, Virginia, United States, 23502
      • Virginia Eye Consultants
    • Richmond, Virginia, United States, 23238
      • Commonwealth Eye Associates
    • Richmond, Virginia, United States, 23294
      • Eye Care Center of Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Beach Eye Care
  • Washington
    • Federal Way, Washington, United States, 98003
      • Evergreen Eye Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Clinic, Ltd.
    • Madison, Wisconsin, United States, 43715
      • Dean Foundation for Health, Research and Education, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria (all subjects):

1. Be at least 12 years of age, male or female, of any race;
2. Provide written informed consent and sign a HIPAA form. Patients who are under the age of 18 will need to sign an assent form as well as having a parent or legal guardian sign an informed consent;
3. Willingness and ability to follow all instructions and comply with schedule for follow-up visits;
4. For females capable of becoming pregnant, agree to have urine pregnancy testing performed prior to randomization of the study eye and on the day of the fellow eye treatment (which occurs between the 3 to 6 month study eye visits); must not be lactating, and must agree to use a medically acceptable form of birth control for at least one week prior to the randomization visit and continue to use the method until one month after the last dose of test article. Acceptable forms for birth control are spermicide with barrier, oral contraceptive, injectable or implantable method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of partner. For non-sexually active females, abstinence will be considered an acceptable form of birth control. Women considered capable of becoming pregnant include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (e.g. hysterectomy, bilateral tubal ligation, or bilateral oophorectomy);
5. BSCVA of ≥1 letter and ≤80 letters on ETDRS chart;
6. Presence of central or inferior steepening on the topographic map;
7. Contact Lens Wearers Only: Removal of contact lenses is required for a 1 week period prior to the screening visit(s);

8. Contact Lens Wearers Only: manifest refraction must be stable between two visits which occur at least 7 days apart. A stable refraction is one in which the manifest refraction spherical equivalent and the average K (Km) on the topographer taken at the first visit do not differ by more than 0.75 D from the respective measurements taken at the second exam;

   Inclusion Criteria (keratoconus subjects only):

9. Have a maximum corneal curvature as measured by Kmax of ≥ 47.00 D;

10. Having topographic evidence of keratoconus with a diagnosis of mild, moderate or severe keratoconus defined as the following:

    • Mild Keratoconus

      1. Axial topography consistent with keratoconus
      2. Flat keratometry reading ≤ 51.00 D on topography map

    • Moderate Keratoconus

      1. Axial topography consistent with keratoconus
      2. Flat keratometry reading ≥ 51.01 D and ≤ 56.00 D or astigmatism ≥ 8.00D on topography map

    • Severe Keratoconus:

      1. Axial topography consistent with keratoconus with marked areas of steepening
      2. Flat keratometry reading ≥ 56.01 D on topography map

    Inclusion Criteria (corneal ectasia subjects only):

11. Having a diagnosis of corneal ectasia after refractive surgery;
12. Having axial topography consistent with ectasia;

Exclusion Criteria (all subjects):

1. Contraindications, sensitivity or known allergy to the test article(s) or their components;
2. If female, be pregnant, nursing or planning a pregnancy or have a positive urine pregnancy test prior to the randomization or treatment of either eye or during the course of the study;
3. Corneal pachymetry that is < 375 microns prior to epithelial debridement at the thinnest point in the eye to be treated;
4. Eyes which are aphakic;
5. Eyes which are pseudophakic and do not have a UV blocking lens implanted;

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

   1. History of corneal disease (e.g., herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, corneal melt, corneal dystrophy, etc.)
   2. Clinically significant corneal scarring in the cross-linking treatment zone that is not related to keratoconus or corneal ectasia, in the investigator's opinion, will interfere with the cross-linking procedure;
7. A history of delayed epithelial healing in the eye(s) to be treated;
8. Patients with nystagmus or any other condition that would prevent a steady gaze during the treatment or other diagnostic tests;
9. Patients with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing;
10. Taking Vitamin C (ascorbic acid) supplements within 1 week of the cross-linking treatment.
11. A history of previous corneal crosslinking treatment in the eye to be treated;
12. Have used an investigational drug or device within 30 days of the study or be concurrently enrolled in another investigational drug or device trial within 30 days of the study;
13. A history of previous corneal surgery (other than LASIK or PRK for subjects with corneal ectasia) or the insertion of Intacs in the eye(s) to be treated;
14. A history of previous Limbal Relaxing Incision (LRI) procedure in the eye(s) to be treated;

15. In addition, the Investigator may exclude or discontinue any subject for any sound medical reason;

    Exclusion Criteria (Keratoconus subjects only):

16. Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VibeX Treatment Group A; Corneal collagen cross-linking using riboflavin ophthalmic solution and ultraviolet-A (UVA) light for 8 minutes	Device: KXL System (15 mW/cm2); UVA irradiation for 8 minutes at 15 mW/cm2; Drug: riboflavin ophthalmic solution; Drops of riboflavin ophthalmic solution will be applied in the eye every two minutes for 20 minutes; Other Names: VibeX
Active Comparator: VibeX Treatment Group B; Corneal collagen cross-linking using riboflavin ophthalmic solution and ultraviolet-A (UVA) light for 4 minutes	Drug: riboflavin ophthalmic solution; Drops of riboflavin ophthalmic solution will be applied in the eye every two minutes for 20 minutes; Other Names: VibeX; Device: KXL System (30 mW/cm2); UVA irradiation for 4 minutes at 30 mW/cm2
Active Comparator: VibeX Treatment Group C; Corneal collagen cross-linking using riboflavin ophthalmic solution and ultraviolet-A (UVA) light for 2 minutes and 40 seconds	Drug: riboflavin ophthalmic solution; Drops of riboflavin ophthalmic solution will be applied in the eye every two minutes for 20 minutes; Other Names: VibeX; Device: KXL System (45 mW/cm2); UVA irradiation for 2 minutes 40 seconds at 45 mW/cm2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change in maximum corneal curvature (Kmax) from baseline	Month 6 or 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of treatment groups within each treatment indication	Month 6 and 12

Collaborators and Investigators

• Sponsor: American-European Congress of Ophthalmic Surgery
• Investigators: Principal Investigator: John Vukich, MD, American-European Congress of Ophthalmic Surgery

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: October 24, 2011
• First Posted (Estimate): October 26, 2011

Study Record Updates

• Last Update Posted (Actual): July 5, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Pathological Conditions, Anatomical; Keratoconus; Dilatation, Pathologic; Corneal Diseases; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Pharmaceutical Solutions; Ophthalmic Solutions; Riboflavin
• Other Study ID Numbers: ACOS-KXL-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No