ExCrossV Multi Site Trial for Vascularized High Risk Keratoplasty

Phase 2

Not yet recruiting

• Conditions: Corneal Transplant Failure

• Registration Number: NCT06753916
• Lead Sponsor: Massachusetts Eye and Ear Infirmary

Brief Summary

The main objective of this study is to determine the safety of Ex Vivo Cross Linking (CXL) of donor corneal tissue in participants who have undergone high-risk penetrating keratoplasty.

Detailed Description

This is a randomized, double-masked, multi site clinical trial to determine the safety of Ex Vivo CXL of donor corneal tissue in 96 participants who have undergone high-risk penetrating keratoplasty.

Participants will be randomized to receive either a corneal tissue that has been untreated vs. a corneal tissue that has been treated with Photrexa® Viscous \& Photrexa® and UV light. The tissue will be prepared by a Corneal Tissue Bank under Current-Good-Tissue-Practice (CGTP) and delivered to the respective institutions for transplantation. Participants will be monitored up to 24 months post-transplantation to assess for adverse events of the randomized tissue.

Study Timeline

• Study First Submitted: 2024-09-19
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-20
• Last Update Submitted: 2024-12-20
• Study First Posted: 2024-12-31
• Last Update Posted: 2024-12-31
• Study Start: 2025-01-01
• Primary Completion: 2028-01-01
• Study Completion: 2031-01-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

• Age 18 and older
• Willing and able to provide written informed consent
• Willing and able to comply with study assessments for the full duration of the study
• Patients undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft
• Superficial vessels are defined as those within the anterior one-third of the cornea and deep vessels within the posterior two-thirds of the cornea (i.e., deep stroma).

Superficial CNV involving ≤2 quadrants (equivalent to ≤6 clock hours) without deep CNV are classified as mild. CNV with >2 quadrants of superficial vessels (>6 clock hours) or 1 quadrant of deep vessels (>3 clock hours) as severe (36).

Exclusion Criteria

• History of Stevens-Johnson syndrome or ocular pemphigoid
• Ocular or periocular malignancy
• Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
• Uncontrolled glaucoma
• Change in topical corticosteroid regimen within 14 days of transplantation
• Use of systemic immunosuppressive for indication other than corneal graft rejection
• Participation in another simultaneous medical investigation or trial
• Pregnancy (positive pregnancy test) or lactating
• Pre-menopausal women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)
• Ocular infection within 30 days prior to study entry.
• Presence of anterior chamber intraocular lens
• Active uveitis within 90 days prior to the study entry.
• No ocular surgery or procedure within 90 days prior to the study entry or concomitant to the study procedure.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Determining the Primary Safety of Corneal Cross Linking	24 Months	The occurrence of adverse events throughout study including: 1. Ocular Safety per the incidences and severity of ocular adverse events during the study based on ophthalmic examination and participants' self-report.; 2. Short Term Safety Events (Post Surgery \< 1 Month); * Post-Op Microbial Keratitis; * Acute Rejection (Epithelial, Endothelial, Sub epithelial, or Mixed); 3. Long Term Safety Events (Post Surgery \> 1 Month); * Rejection (Epithelial, Endothelial, or Mixed); * Graft Failure; * Ulcerative Keratitis; * Persistent Epithelial Defect lasting more than 6 Weeks

Secondary Outcome Measures

Name	Time	Method
Measure of the Frequency of Graft Failures though Corneal Cross Linking	24 Months	To determine the efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization, by measuring the frequency of primary graft failures over 24 months.
Measure of Time from Surgery to Overall Graft Failure for Corneal Cross Linking over 24 Months	24 Months	The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization, by measuring the time from surgery to overall graft failure (regardless of cause).
Measure of Time from Surgery to Graft Rejection for Corneal Cross Linking over 24 Months	24 Months	The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization, by measuring the occurrence of any rejection episode. (Epithelial, Endothelia, Sub Epithelial, or Mixed) determined as either definite rejection, probably rejection, and possible rejection, from the time of surgery over 24 months.
Measure of the Efficacy of Corneal Cross Linking Through Image Review	24 Months	The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization.; 1. Corneal Neovascularization (CNV) measured and analyzed from slit-lamp photography.

Trial Locations

Locations (10)

University of California Irvine - Gavin Herbert Eye Institute; 🇺🇸 Irvine, California, United States

The University of California Los Angeles - Doris Stein Eye Research Center; 🇺🇸 Los Angeles, California, United States

University of Miami - Bascom Palmer Eye Institute; 🇺🇸 Miami, Florida, United States

Price Vision Group; 🇺🇸 Indianapolis, Indiana, United States

Massachusetts Eye and Ear; 🇺🇸 Boston, Massachusetts, United States

University of Michigan - Kellogg Eye Center; 🇺🇸 Ann Arbor, Michigan, United States

Wake Forest Baptist Eye Center; 🇺🇸 Bermuda Run, North Carolina, United States

Duke University - Duke Eye Center; 🇺🇸 Durham, North Carolina, United States

Cincinnati Eye Institute; 🇺🇸 Cincinnati, Ohio, United States

Oregon Health and Science University - Casey Eye Institute; 🇺🇸 Portland, Oregon, United States