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

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

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.

Study Overview

• Status: Completed
• Conditions: Corneal Ulcer; Leukoma
• Intervention / Treatment: Device: Collagen-MPC cornea

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ukraine
  • Odessa, Ukraine, 65061
    • The Filatov Institute of Eye Diseases and Tissue Therapy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must sign and be given a copy of the written Informed Consent form.
2. 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.
3. Subjects must be willing and able to return for scheduled follow-up examinations for 12 months after surgery.

Exclusion Criteria:

1. Subjects with severe or life-threatening systemic disease.
2. Subjects with uncontrolled hypertension.
3. Subjects with uncontrolled diabetes or insulin-dependent diabetes.
4. Subjects with glaucoma in either eye.
5. Subjects with marked microphthalmos or aniridia in either eye.
6. 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.
7. Subjects which are or lactating or who plan to become pregnant over the course of the clinical investigation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Collagen-MPC cornea substitute; Collagen-phosphorylcholine (collagen-MPC) cornea substitute transplantation using anterior lamellar keratoplasty technique.

Device: Collagen-MPC cornea; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Filatov Institute of Eye Diseases and Tissue Therapy
• Collaborators: Linkoeping University
• Investigators: Study Director: Nataliya Pasyechnikova, MD, PhD, DSc, The Filatov Institute of Eye Diseases and Tissue Therapy

Publications and helpful links

General Publications

• Liu W, Deng C, McLaughlin CR, Fagerholm P, Lagali NS, Heyne B, Scaiano JC, Watsky MA, Kato Y, Munger R, Shinozaki N, Li F, Griffith M. Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes. Biomaterials. 2009 Mar;30(8):1551-9. doi: 10.1016/j.biomaterials.2008.11.022. Epub 2008 Dec 20.
• Hackett JM, Lagali N, Merrett K, Edelhauser H, Sun Y, Gan L, Griffith M, Fagerholm P. Biosynthetic corneal implants for replacement of pathologic corneal tissue: performance in a controlled rabbit alkali burn model. Invest Ophthalmol Vis Sci. 2011 Feb 3;52(2):651-7. doi: 10.1167/iovs.10-5224.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: October 26, 2014
• First Submitted That Met QC Criteria: October 27, 2014
• First Posted (Estimate): October 28, 2014

Study Record Updates

• Last Update Posted (Actual): October 26, 2018
• Last Update Submitted That Met QC Criteria: October 25, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Eye Diseases; Keratitis; Corneal Diseases; Eye Infections; Corneal Ulcer
• Other Study ID Numbers: 03/2013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No