EVOKE: Safety and Efficacy of Ex Vivo Corneal Cross-Linking of Donor Corneal Tissue Used For a Penetrating Keratoplasty

Sponsor

Joseph B. Ciolino, MD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04584125

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This research study will assess the safety and efficacy of crosslinking donor corneal tissue in participants who have undergone corneal transplantation for keratoconus. Crosslinking is a procedure that stabilizes the biomechanical properties of the cornea; as a result, the cornea stiffens. It has been shown that this procedure stabilizes the cornea of patients with keratoconus or corneal ectasias. The FDA currently approves crosslinking for patients with progressive keratoconus and corneal ectasia following refractive surgery. Keratoconus has been found to recur in corneas that underwent corneal transplantation. Ex vivo crosslinking of donor corneal tissue for patients with keratoconus undergoing penetrating keratoplasty could stabilize the cornea and reduce the risk of recurrence of keratoconus.

Condition or Disease	Intervention/Treatment	Phase
Keratoconus	Drug: Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146%	Early Phase 1

Detailed Description

In this study, ten patients with keratoconus who will undergo their first corneal transplant surgery in the study eye will be included. When a screened participant meets the inclusion and exclusion criteria to be enrolled in the study, the investigator will request a cornea from the central eye bank. The eye bank will then prepare and crosslink the corneal tissue with riboflavin (Vitamin B2) and ultraviolet A (UVA) light. This prepared corneal tissue will be used for the corneal transplant of the patients. Subjects will be followed up post-operatively by the site investigators with a follow-up period of 24 months and standard of care follow-up every six months for up to 3 years or until study closure. The investigators will monitor for systemic and ocular adverse events at all follow-up visits.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an open-label, single-center, pilot clinical trial to assess the safety and efficacy of ex vivo corneal crosslinking of donor corneal tissue used for penetrating keratoplasty in patients with keratoconus. The study will include 10 participants; these individuals will receive the previously crosslinked corneal tissue for their corneal transplant. Participants will receive close follow-up for up to two years for evaluation of safety and efficacy.This is an open-label, single-center, pilot clinical trial to assess the safety and efficacy of ex vivo corneal crosslinking of donor corneal tissue used for penetrating keratoplasty in patients with keratoconus. The study will include 10 participants; these individuals will receive the previously crosslinked corneal tissue for their corneal transplant. Participants will receive close follow-up for up to two years for evaluation of safety and efficacy.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open-Label Pilot Clinical Trial to Evaluate the Safety and Efficacy of Ex Vivo Corneal Cross-Linking of Donor Corneal Tissue Used for a Penetrating Keratoplasty in Keratoconus Patients

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ex vivo cross linking of donor corneal tissue The donor corneal tissue used in the penetrating keratoplasty procedures will previously undergo ex vivo crosslinking.	Drug: Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% A wavelength of 365 nm ultraviolet A light will be used to direct 5.4 J/cm2 using a beam diameter of 9.5mm to treat the de-epithelialized corneal surface of a donor cornea for 30 minutes. Every 5 minutes, the UV light will be used while another drop of riboflavin is applied on top of the donor cornea. Other Names: PHOTREXA VISCOUS

Arm

Intervention/Treatment

Experimental: Ex vivo cross linking of donor corneal tissue

The donor corneal tissue used in the penetrating keratoplasty procedures will previously undergo ex vivo crosslinking.

Drug: Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146%

A wavelength of 365 nm ultraviolet A light will be used to direct 5.4 J/cm2 using a beam diameter of 9.5mm to treat the de-epithelialized corneal surface of a donor cornea for 30 minutes. Every 5 minutes, the UV light will be used while another drop of riboflavin is applied on top of the donor cornea.

Other Names:

PHOTREXA VISCOUS

Outcome Measures

Primary Outcome Measures

Incidence of treatment-emergent adverse events as assessed by ocular infection, delayed wound healing time, or graft rejection [24 months]
Safety assessed by the occurrence of the following adverse events: post-operative microbial keratitis, graft rejection or failure, delayed wound healing greater than 4 weeks, or ulcerative keratitis

Secondary Outcome Measures

Efficacy assessed by refractive measurements [24 months]
Effectiveness assessed by refractive and topographic astigmatism
Efficacy assessed by tomography [24 months]
Effectiveness assessed by the stability of tomographic measurements: maximum keratometry, anterior mean keratometry, posterior mean keratometry
Efficacy assessed by visual acuity [24 months]
Effectiveness assessed by best spectacle-corrected visual acuity
Efficacy assessed by the need for rigid gas permeable contact lens [24 months]
Effectiveness assessed by the percent of participants that require rigs gas permeable contact lens.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 but ≤50 years
History of keratoconus (without a previous transplant) requiring a penetrating keratoplasty
Willing to commit to not having further cross-linking, corneal relaxing incisions, intacs, or corneal laser vision correction during the course of the study

Exclusion Criteria:

Age < 18 years >50
Inability to provide written informed consent and comply with study assessments for the full duration of the study
Participation in another simultaneous interventional medical investigation or trial

Systemic

History of Stevens-Johnson syndrome or ocular pemphigoid
Signs of current infection, including fever and current treatment with antibiotics
Pregnancy (positive pregnancy test) or lactating
Pre-menopausal sexually active women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)

Recipient Eye

Corneal or ocular surface infection within 30 days prior to study entry
History of previous cross-linking
History of previous corneal transplant
Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
Ocular or periocular malignancy
Lid abnormalities that in the opinion of the investigator could confound the study results and these include clinically significant ectropion, lagophthalmos, cicatrization, entropion, and rosacea
Neurotrophic cornea
Monocular
Uncontrolled glaucoma
Glaucoma filtering devices or trabeculectomies