Safety and Effectiveness of Collagen-phosphorylcholine Bioengineered Cornea in Patients Requiring Lamellar Keratoplasty

Study Overview
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Brief Summary
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In this study the safety and effectiveness of biosynthetic cornea, comprising interpenetrating networks of recombinant human collagen and phosphorylcholine, will be tested in patients with severe corneal pathology (corneal ulcers or corneal opacification from corneal injury, burn or infection) - diseases, where human donor cornea transplantation (the only widely accepted treatment) carries a high risk of rejection.

Detailed Description
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Collagen-phosphorylcholine corneal substitute will be implanted in patient's corneas with severe pathology (corneal ulcer, corneal leukoma after burn, trauma or infection) using anterior lamellar keratoplasty technique, i.e. when patient's diseased cornea is removed it will be substituted with proposed transparent implant. Usually these patients are grafted with human donor cornea, but the latter frequently fails due to graft-versus-host problems. We will test the safety (incidence of adverse events, biocompatability) and the effectiveness (ability to promote healing and increase vision) of developed biosynthetic corneas in 10 patients with corneal pathology, where human donor cornea carries a high risk of rejection. The patients will be follow-uped for 12 months.

Official Title
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A Clinical Trial to Evaluate the Safety and Effectiveness of the Collagen-phosphorylcholine Corneal Substitutes in Patients Requiring Lamellar Keratoplasty

Conditions
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Corneal Ulcer, Leukoma

Intervention / Treatment
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* Device: Collagen-MPC cornea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must sign and be given a copy of the written Informed Consent form. Subjects with best corrected distance visual acuity 20/200 or worse as a result of corneal ulcer or corneal scar due to burn, injury or infection in the operative eye. Subjects must be willing and able to return for scheduled follow-up examinations for 12 months after surgery. Exclusion Criteria: Subjects with severe or life-threatening systemic disease. Subjects with uncontrolled hypertension. Subjects with uncontrolled diabetes or insulin-dependent diabetes. Subjects with glaucoma in either eye. Subjects with marked microphthalmos or aniridia in either eye. Subjects with any other serious ocular pathology, serious ocular complications at the time of corneal transplant underlying serious medical conditions, based on the investigator's medical judgment. Subjects which are or lactating or who plan to become pregnant over the course of the clinical investigation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Collagen-MPC cornea substitute<br>Collagen-phosphorylcholine (collagen-MPC) cornea substitute transplantation using anterior lamellar keratoplasty technique. | Device: Collagen-MPC cornea<br>* Patients will undergo surgery using conventional anterior lamellar keratoplasty technique: diseased cornea will be trephined to approximately 50-90% of corneal thickness (depending on corneal ulcer or scar depth) and then a lamellar dissection will be created. Trephine diameter will depend on ulcer or leukoma maximal size. Alternatively a femtosecond laser may be used to create the dissection. A collagen-phosphorylcholine cornea 250-500 microns thick and equal or 0.25 mm larger diameter is placed and sutured. The sutures are superimposed and the implant and the sutures covered with a bandage contact lens. The sutures and bandage lens will be removed later after the initial healing period of 4 weeks or as determined by physician depending on the implant epithelial coverage.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events | Implant safety and tolerability will be measured by absence/presence of its lysis as well as by degree of eye inflammation based on conjunctival injection, perifocal corneal haze, aqueous humor transparency, increased intraocular pressure and self reported postoperative pain. Each item is scored 0-4: 0 = no symptom, 4 = severe symptom. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Healed Cornea at 12 Months | Cornea is considered to have healed up when there is no defect of corneal epithelium, which is confirmed by fluorescein staining of corneal surface | 12 months | 
| Number of Participants With Improved Visual Acuity at 12 Months | Improvement of 1 or more lines in Corrected Distance Visual Acuity in comparison to preoperative visual acuity | 12 months |