A Multi-Center, Randomized, Placebo-Controlled Evaluation of the Safety and Efficacy of the KXL System With VibeX (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in Eyes With Keratoconus

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Avedro, Inc.
ClinicalTrials.gov Identifier:
NCT01972854
First received: October 25, 2013
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Keratoconus
Drug: riboflavin: 0.12% riboflavin ophthalmic solution with the KXL system
Drug: placebo: 0.0% riboflavin opthalmic solution with the KXL system
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-Center, Randomized, Placebo-Controlled Evaluation of the Safety and Efficacy of the KXL System With VibeX (Riboflavin Ophthalmic Solution) for Corneal Collagen Cross-Linking in Eyes With Keratoconus

Resource links provided by NLM:


Further study details as provided by Avedro, Inc.:

Primary Outcome Measures:
  • Change in Kmax from baseline [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The primary endpoint is the mean change from baseline to 12 months in maximum corneal curvature (Kmax) between the VibeX treatment group and the Placebo control group.

  • Safety Endpoints [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    1. Loss of BSCVA (Best Spectacle-Corrected Visual Acuity) beginning at the 6 month follow-up examination, specifically, the percentage of eyes that have a loss of 15 or more letters in BSCVA on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart as compared to baseline
    2. The incidence of serious ophthalmic adverse events


Estimated Enrollment: 206
Study Start Date: November 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0.12% riboflavin ophthalmic solution Drug: riboflavin: 0.12% riboflavin ophthalmic solution with the KXL system
Subjects will receive 0.12% riboflavin ophthalmic solution (VibeX) followed by irradiation with the KXL System at 30mW/cm2 intensity for 8 minutes with an on/off cycle of 1 second UVA on/1 second UVA off, for a total radiant exposure of 7.2 J /cm2.
Placebo Comparator: Placebo 0.0% riboflavin ophthalmic solution Drug: placebo: 0.0% riboflavin opthalmic solution with the KXL system
Subjects will receive 0.0% riboflavin ophthalmic solution (Placebo) followed by irradiation with the KXL System at 30mW/cm2 intensity for 8 minutes with an on/off cycle of 1 second UVA on/1 second UVA off, for a total radiant exposure of 7.2 J /cm2.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must meet all of the following criteria in order to be enrolled in the trial:

  1. Be at least 12 years of age, male or female, of any race;
  2. Provide written informed consent and sign a HIPAA form. Subjects who are under the age of 18 (or have not yet reached the age of majority per local regulations) 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, including the ability to read English to complete the NEI-VFQ 25 questionnaire;
  4. For females capable of becoming pregnant, agree to have urine pregnancy testing performed at Visit 2 prior to randomization of the study eye and prior to treatment of a fellow and/or cross-over eye; must not be lactating, and must agree to use a medically acceptable form of birth control for at least one week prior to Visit 2, one week prior to treatment of a fellow eye or cross-over eye, and continue to use the method for one month following the last treatment. 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. Subjects > 25 years old at the time of screening of their study eye must meet the following criteria. Subjects ≤ 25 years old and all subjects who have their fellow-eye or crossover eye treated are not required to meet these criteria;

    - Having a diagnosis of progressive keratoconus defined as one or more of the following changes over a period of 36 months or less:

    1. An increase of ≥ 1.00 D in the steepest keratometry value (ksteep)
    2. An increase of ≥ 1.00 D in regular astigmatism evaluated by subjective manifest refraction or as evaluated by comparing eyeglass or contact lens prescriptions to current subjective manifest refraction
    3. A myopic shift (decrease in the spherical equivalent) of ≥ 0.50 D in subjective manifest refraction or as evaluated by comparing eyeglass or contact lens prescriptions to current subjective manifest refraction
    4. A decrease ≥ 0.1 mm in the BOZR (Back Optical Zone Radius) in rigid contact lens wearers where other information is not available
  6. 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 Pentacam keratometry reading ≤ 51.00D
    • Moderate Keratoconus:

      1. Axial topography consistent with keratoconus
      2. Flat Pentacam keratometry reading > 51.00 D and ≤ 56.00 D or astigmatism ≥ 8.00 D
    • Severe Keratoconus:

      1. Axial topography consistent with keratoconus with marked areas of steepening
      2. Flat Pentacam keratometry reading > 56.00 D
  7. Presence of central or inferior steepening on the Pentacam map;
  8. Have a maximum corneal curvature, as measured by Kmax, of ≥ 47.00 D;
  9. BSCVA of ≥ 1 letter and ≤ 80 letters on ETDRS chart;
  10. Contact Lens Wearers Only: Removal of contact lenses is required for a 1 week period prior to the first screening refraction visit (and each subsequent Visit 1, as necessary) and must remain out until the 1 month visit is completed;
  11. Contact Lens Wearers Only: Manifest refraction must be stable between two consecutive 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 Pentacam taken at the first visit do not differ by more than 0.75 D from the respective measurements taken at the second exam. A contact lens wearer is defined as someone who has worn contact lenses in the eye to be treated in the last 30 days.

Exclusion Criteria:

Subjects must not meet any of the following criteria to be enrolled in the trial:

  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 during the course of the study or have a positive urine pregnancy test at Visit 2 prior to randomization or treatment of either eye;
  3. Eyes classified as either normal, atypical normal, or keratoconus suspect on the severity grading scheme;
  4. A history of previous corneal surgery or the insertion of Intacs in the eye to be treated;
  5. A history of previous Limbal Relaxing Incision (LRI) procedure in the eye to be treated;
  6. Corneal pachymetry that is < 375 microns prior to epithelial debridement at the thinnest point measured by Pentacam in the eye to be treated;
  7. Eyes which are aphakic;
  8. Eyes which are pseudophakic and do not have a UV blocking lens implanted;
  9. 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 or evidence of active or inactive corneal disease (e.g., herpes simplex keratitis, herpes zoster keratitis, corneal melt, recurrent corneal erosion syndrome, corneal dystrophy, etc.);
    2. Clinically significant corneal scarring in the cross-linking treatment zone that is not related to keratoconus or, in the investigator's opinion, will interfere with the cross-linking procedure;
  10. A history of delayed epithelial healing in the eye to be treated;
  11. Subjects with nystagmus or any other condition that would prevent a steady gaze during the treatment or other diagnostic tests;
  12. Subjects with a current condition that, in the investigator's opinion, would interfere with or prolong epithelial healing;
  13. Taking supplements containing Vitamin C (ascorbic acid) within 1 week of the cross-linking treatment;
  14. A history of previous corneal crosslinking treatment in the eye to be treated;
  15. The subject should not have participated in any investigational drug or device study within 30 days of screening or be concurrently enrolled in another investigational drug or device study.
  16. The Investigator may exclude or discontinue any subject for any sound medical reason.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01972854

Locations
United States, California
UC Irvine Department of Ophthalmology
Irvine, California, United States, 92868
Gordon -Weiss Vision Institute
San Diego, California, United States, 92122
United States, Indiana
Price Vision Group
Indianapolis, Indiana, United States, 46260
United States, Kansas
Durrie Vision
Overland Park, Kansas, United States, 66211
United States, Massachusetts
Ophthalmic Consultants of Boston
Waltham, Massachusetts, United States, 02451
United States, New Jersey
Hersh Vision Group
Teaneck, New Jersey, United States, 07666
United States, Pennsylvania
UPMC Eye Center
Pittsburgh, Pennsylvania, United States, 15213
United States, South Dakota
Vance Thompson Vision
Sioux Falls, South Dakota, United States, 57105
United States, Texas
Focal Point Vision
San Antonio, Texas, United States, 78229
United States, Utah
Hoopes Vision
Draper, Utah, United States, 84020
United States, Virginia
See Clearly Vision
McLean, Virginia, United States, 22102
Sponsors and Collaborators
Avedro, Inc.
  More Information

No publications provided

Responsible Party: Avedro, Inc.
ClinicalTrials.gov Identifier: NCT01972854     History of Changes
Other Study ID Numbers: KXL-005
Study First Received: October 25, 2013
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Avedro, Inc.:
keratoconus
cross-linking
KXL

Additional relevant MeSH terms:
Keratoconus
Corneal Diseases
Eye Diseases
Ophthalmic Solutions
Riboflavin
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Photosensitizing Agents
Dermatologic Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014