Vision Restoration With a Collagen Crosslinked Boston Keratoprosthesis Unit

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Keratolysis

Intervention / Treatment
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* Drug: Riboflavin
* Drug: Dextran
* Device: UVA Light Source


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment Arm<br>De-epithelialized corneas cross-linked with riboflavin 0.1% and dextran 20% solution AND ultraviolet A light (UVA Light Source). | Drug: Riboflavin<br>* Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.<br>* Other names: Vitamin B2;Drug: Dextran<br>* Dextran is used to increase the viscosity of the solution.<br>* Other names: Gentran 70, Hyskon;Device: UVA Light Source<br>* 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.<br>* Other names: KXL® System;|
| Active Comparator: Control Treatment Arm<br>De-epithelialized corneas will be exposed to only riboflavin 0.1% with dextran 20% solution (NO ultraviolet A light). | Drug: Riboflavin<br>* Riboflavin, a water soluble vitamin, is an essential nutrient and a natural component of many foods.<br>* Other names: Vitamin B2;Drug: Dextran<br>* Dextran is used to increase the viscosity of the solution.<br>* Other names: Gentran 70, Hyskon;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Keratolysis, Corneal Melting, Boston KPro, Keratoprosthesis