Corneal Transplant FailurePhase 2ExCrossVNCT06753916
ExCrossV Multi Site Trial for Vascularized High Risk Keratoplasty
A Phase 2 study testing Corneal Donor Tissue with Cross Linking and Corneal Donor Tissue without Cross Linking in people with Corneal Transplant Failure, run by Massachusetts Eye and Ear Infirmary at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Transplant Failure
- What is being tested?
- Corneal Donor Tissue with Cross Linking and Corneal Donor Tissue without Cross Linking
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 12 sitesUnited States
- Study dates
- 1 Apr 2025to 1 Jan 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Nikolay Boychev, OD, PhD contact
12 sites in 1 country
United States12 sites, 12 recruiting
- Recruiting
University of Michigan - Kellogg Eye Center
Ann Arbor, Michigan, 48015
Lianne Shami, BS, 734-647-8397, liannes@med.umich.edu
Shahzad Mian, MD
- Not yet recruiting
Wake Forest Baptist Eye Center
Bermuda Run, North Carolina, 27006
Christina Robbins, 336-716-3859, Christina.Robbins@Advocatehealth.org
Matthew Giegengack, MD
- Recruiting
Massachusetts Eye and Ear
Boston, Massachusetts, 02114
Michael Cheung, MSc, CCRP, 617-573-6060, mcheung0@meei.harvard.edu
Nikolay Boychev, OD, PhD, nboychev@meei.harvard.edu
- Recruiting
Cincinnati Eye Institute
Cincinnati, Ohio, 45242
Lee Stokes, 513-569-3213, lstokes@cvphealth.com
Kavitha Sivaraman, MD
- Recruiting
Duke University - Duke Eye Center
Durham, North Carolina, 27705
Nathan Hamilton, 919-668-0230, nathan.hamilton@duke.edu
Kyle Munar, kyle.munar@duke.edu
- Recruiting
Price Vision Group
Indianapolis, Indiana, 46260
Marianne Price, PhD, 317-844-5530, mprice@cornea.org
Lauren Blisset, (317) 814-2996, lauren@cornea.org
- Not yet recruiting
University of California Irvine - Gavin Herbert Eye Institute
Irvine, California, 92617
Marjan Farid, MD
- Not yet recruiting
The University of California Los Angeles - Doris Stein Eye Research Center
Los Angeles, California, 90095
Anthony Aldave, MD
- Recruiting
University of Miami - Bascom Palmer Eye Institute
Miami, Florida, 33136
Jeremy Sandoval, jxs7997@med.miami.edu
Javier Parades, MBA, CCRP, jxp2537@med.miami.edu
- Recruiting
Kansas City Eye Clinic
Overland Park, Kansas, 66204
Megan Hefer, CCRP, 913-341-3100, mhefter@kceyeclinic.com
Christopher Ketcherside, MD
- Not yet recruiting
University of California San Francisco - Wayne and Gladys Valley Center for Vision
San Francisco, California, 94158
Beth Cutrer, Beth.Cutrer@ucsf.edu
Julie Schallhorn, MD
- Recruiting
Mid-Atlantic Cornea Consultant
Towson, Maryland, 21204
Lauren West, 410-616-9952, lwest@midatlanticcornea.com
Alexander Altman, MD
About this study
Official title: Multicenter Clinical Trial to Evaluate the Safety and Efficacy of Ex Vivo Corneal Cross-linking of Donor Corneal Tissue Used for Vascularized High-risk Keratoplasty
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.
Read the 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.
- Conditions
- Corneal Transplant Failure
- Being tested
- Corneal Donor Tissue with Cross Linking, Corneal Donor Tissue without Cross Linking
- Keywords
- Keratoplasty, Cross Linking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Corneal Donor Tissue with Cross LinkingProcedure or surgery
Also called Treatment
Participants are transplanted with corneal donor tissue that has been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® Viscous \& Photrexa®) with UV light treatment.
Corneal Donor Tissue without Cross LinkingProcedure or surgery
Also called Control
Participants are transplanted with corneal donor tissue that has not been treated with the UV light and the 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® Viscous \& Photrexa®) without UV light treatment, this is the control group.
| Study group | Role | What they receive |
|---|---|---|
| Participants Receiving Treated Cross Linked Corneal Tissue | Experimental | Participants in this group will receive tissue that has been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® viscous and Photrexa®) with UV light treatment. Participants will be monitored over a period of 24 months. Receives: Procedure: Corneal Donor Tissue with Cross Linking |
| Participants Receiving Untreated Cross Linked Corneal Tissue | Placebo comparator | Participants in this group will receive tissue that has has not been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® viscous and Photrexa®) without UV light treatment. Participants will be monitored over a period of 24 months. Receives: Procedure: Corneal Donor Tissue without Cross Linking |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determining the Primary Safety of Corneal Cross Linking
The occurrence of adverse events throughout study including:
- Ocular Safety per the incidences and severity of ocular adverse events during the study based on ophthalmic examination and participants' self-report.
- Short Term Safety Events (Post Surgery < 1 Month)
- Post-Op Microbial Keratitis
- Acute Rejection (Epithelial, Endothelial, Sub epithelial, or Mixed)
- 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
Measured: 24 Months
Secondary outcomes (4)
Measure of the Frequency of Graft Failures though Corneal Cross Linking
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.
Measured: 24 Months
Measure of Time from Surgery to Overall Graft Failure for Corneal Cross Linking over 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).
Measured: 24 Months
Measure of Time from Surgery to Graft Rejection for Corneal Cross Linking over 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.
Measured: 24 Months
Measure of the Efficacy of Corneal Cross Linking Through Image Review
The efficacy of using cross linked tissue for the indicated keratoplasty for the prevention of corneal graft rejection and corneal neovascularization.
- Corneal Neovascularization (CNV) measured and analyzed from slit-lamp photography.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2024
- Study start1 Apr 2025
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Corneal Transplant FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph B. Ciolino, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Joseph Ciolino, MD, Principal investigator, Massachusetts Eye and Ear
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06753916
- Sponsor's protocol ID
- 2023P002687
- Acronym
- ExCrossV
- Status last verified
- Sep 2026
- First submitted
- 19 Sep 2024
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Clinical Trial to Evaluate the Safety and Efficacy of Ex Vivo Corneal Cross-linking of Donor Corneal Tissue Used for Vascularized High-risk Keratoplasty
- ClinicalTrials.gov ID
- NCT06753916
- Acronym / sponsor ID
- ExCrossV / 2023P002687
- Conditions
- Corneal Transplant Failure
- Keywords
- Keratoplasty, Cross Linking
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Study start
- 1 Apr 2025 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Jan 2031 (estimated)
- First posted
- 31 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Participants Receiving Treated Cross Linked Corneal Tissue | Experimental | Procedure: Corneal Donor Tissue with Cross LinkingParticipants in this group will receive tissue that has been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® viscous and Photrexa®) with UV light treatment. Participants will be monitored over a period of 24 months. |
| Participants Receiving Untreated Cross Linked Corneal Tissue | Placebo comparator | Procedure: Corneal Donor Tissue without Cross LinkingParticipants in this group will receive tissue that has has not been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® viscous and Photrexa®) without UV light treatment. Participants will be monitored over a period of 24 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Corneal Donor Tissue with Cross LinkingAlso: TreatmentParticipants are transplanted with corneal donor tissue that has been treated with 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® Viscous \& Photrexa®) with UV light treatment. | Procedure or surgery | Participants Receiving Treated Cross Linked Corneal Tissue |
| Corneal Donor Tissue without Cross LinkingAlso: ControlParticipants are transplanted with corneal donor tissue that has not been treated with the UV light and the 0.1% riboflavin (Vitamin B2) and 20% dextran (Photrexa® Viscous \& Photrexa®) without UV light treatment, this is the control group. | Procedure or surgery | Participants Receiving Untreated Cross Linked Corneal Tissue |
Primary outcome
Determining the Primary Safety of Corneal Cross Linking
Time frame: 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
4 secondary outcomes
Measure of the Frequency of Graft Failures though Corneal Cross Linking
Time frame: 24 Months
Measure of Time from Surgery to Overall Graft Failure for Corneal Cross Linking over 24 Months
Time frame: 24 Months
Measure of Time from Surgery to Graft Rejection for Corneal Cross Linking over 24 Months
Time frame: 24 Months
Measure of the Efficacy of Corneal Cross Linking Through Image Review
Time frame: 24 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nikolay Boychev, OD, PhD contact
Joseph Ciolino, MD principal investigator
Massachusetts Eye and Ear
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Corneal Donor Tissue with Cross Linking and Corneal Donor Tissue without Cross Linking in people with Corneal Transplant Failure, run by Massachusetts Eye and Ear Infirmary at 12 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Cheung, MSc, CCRP (6175736060, mcheung0@meei.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determining the Primary Safety of Corneal Cross Linking (time frame: 24 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.