Vision Restoration With a Collagen Crosslinked Boston Keratoprosthesis Unit

A Phase I/II Prospective, Randomized, Multicenter, Double-Masked, Vehicle-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Corneal Collagen Cross-Linking of Keratoprosthesis Carrier Tissue in High-Risk Keratoprosthesis Implantation

This is a phase I/II prospective, randomized, multi-center, double-masked, vehicle-controlled clinical trial evaluating the safety and efficacy of corneal collagen cross-linking the keratoprosthesis carrier tissue in subjects who are candidates for high-risk keratoprosthesis implantation but because of a history of corneal melts or autoimmune diseases are not candidate for a traditional corneal transplant.

Study Overview

• Status: Completed
• Conditions: Keratolysis
• Intervention / Treatment: Drug: Riboflavin; Drug: Dextran; Device: UVA Light Source

Detailed Description

The study is a multi-center, parallel, randomized, double-blinded study with subsequent follow-up period of two years. Eight-four subjects across twelve sites will be randomized 1:1 to receive either a corneal tissue that have been cross-linked or not cross-linked (No UVA light source). Cross-linking is a term that refers to the linking of polymers (long chain) molecules by chemical bonds. It is believed that cross-linking the cornea will make the cornea stronger and more resistant to degradation.

CorneaGen (formerly Keralink International) (Baltimore site) will supply the donor tissue and Avedro Inc (Waltham MA) will supply the riboflavin and the UV light source. Staff at CorneaGenwill administer the riboflavin with dextran solution and perform the cross-linking procedure according to one of randomization groups before shipping the masked donor cornea to study sites for Boston Keratoprosthesis (B-KPro) implantation.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-7003
      • The Jules Stein Eye Institute
    • Sacramento, California, United States, 95817
      • UC Davis Health System Eye Center
    • San Diego, California, United States, 92093
      • Shiley Eye Institute, University of California, San Diego
  • Florida
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Illinois Eye and Ear Infirmary
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Cincinnati Eye Institute
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • W.K. Kellogg Eye Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
  • New York
    • New York, New York, United States, 14642
      • David and Ilene Flaum Eye Institute, University of Rochester
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Eye Institute
  • Pennsylvania
    • Bala-Cynwyd, Pennsylvania, United States, 19007
      • Wills Eye
  • Texas
    • Lackland Air Force Base, Texas, United States, 78236
      • Wilford Hall Ambulatory Surgical Center (WHASC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• Willing and able to comply with study assessments for the full duration of the study
• Age ≥ 18 years
• Candidate for a Boston Keratoprosthesis / Cornea transplant
• In generally good stable overall health

• Patients with an eye at risk for a cornea sterile ulcer which includes:

  • Autoimmune diseases (mucus membrane pemphigoid, Stevens-Johnson syndrome, systemic lupus erythematosis, rheumatoid arthritis, or other autoimmune diseases); OR
  • History of previous sterile cornea ulceration requiring a cornea transplant

Exclusion Criteria:

• Age < 18 years
• Inability to provide written informed consent and comply with study assessments for the full duration of the study
• No or minimal tear production with evidence of keratinization of the bulbar conjunctiva
• Corneal or ocular surface infection within 30 days prior to study entry
• Ocular or periocular malignancy
• Inability to wear a contact lens due to lid abnormalities or shortened fornix
• Signs of current infection, including fever and current treatment with antibiotics
• Pregnancy (positive pregnancy test) or lactating
• Participation in another simultaneous interventional medical investigation or trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Treatment Arm; De-epithelialized corneas cross-linked with riboflavin 0.1% and dextran 20% solution AND ultraviolet A light (UVA Light Source).	Drug: Riboflavin; Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.; Other Names: Vitamin B2; Drug: Dextran; Dextran is used to increase the viscosity of the solution.; Other Names: Dextran 70 6% in 0.9%; Sodium Chloride Dextran 70 6% in 5% Dextrose; Gentran 70, Hyskon; Device: UVA Light Source; Avedro's KXL® System is a UVA irradiation system that uses a light emitting diode (LED) to deliver a dose of UVA light to a targeted treatment area for illuminating the cornea during corneal collagen cross-linking.; Other Names: KXL® System
Active Comparator: Control Treatment Arm; De-epithelialized corneas will be exposed to only riboflavin 0.1% with dextran 20% solution (NO ultraviolet A light).	Drug: Riboflavin; Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.; Other Names: Vitamin B2; Drug: Dextran; Dextran is used to increase the viscosity of the solution.; Other Names: Dextran 70 6% in 0.9%; Sodium Chloride Dextran 70 6% in 5% Dextrose; Gentran 70, Hyskon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time From Surgery to Device Loss or Replacement	If the device fails after surgery the time and reason behind the failure will be recorded. The number of device losses in the control group will be compared to the number of device losses in investigational group.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Kpro Retention at 12 Months	The number of participants that retained kpro devices at the end of twelve months will be studied and differences in retention rate between investigational and control groups will be reported	Twelve months
Number of Cumulative Delayed Epithelial Healing Events at Day 30	The number of incidences of delayed epithelial healing at day 30 will be recorded. If there is delayed epithelial healing at day 30 it will be determined if those incidences occurred more often in the control group versus the investigational group.	30 days
Median Time From Surgery to Retroprosthetic Membrane Treatment in Days (Laser or Surgical Interventions)	If follow up surgery is needed to replace or treat the prosthetic the time and reason will be recorded and the number of incidences will be compared between the study treatment groups	2 years
Median Time From Surgery to Occurrence of Vitritis (Sterile or Infectious)	The time (days) and number of incidences of vitritis will be recorded for the subject in which it occurred and the number of incidences will be compared between the study treatment groups.	2 years

Collaborators and Investigators

• Sponsor: Joseph B. Ciolino, MD
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Joseph B. Ciolino, MD, Massachusetts Eye and Ear Infirmary

Publications and helpful links

General Publications

• Davis SA, Bovelle R, Han G, Kwagyan J. Corneal collagen cross-linking for bacterial infectious keratitis. Cochrane Database Syst Rev. 2020 Jun 17;6(6):CD013001. doi: 10.1002/14651858.CD013001.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: June 1, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimate): August 11, 2016

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Keratolysis; Corneal Melting; Boston KPro; Keratoprosthesis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Anticoagulants; Vitamin B Complex; Plasma Substitutes; Blood Substitutes; Riboflavin; Dextrans
• Other Study ID Numbers: 798474

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data within StudyTrax will be extracted at the completion of the study. This data will be held in a secure network file at MEEI for at least two years following a marketing application submission to the FDA or longer, if required by the MEEI IRB.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes