Safety and Effectiveness of the PXL Platinum 330 System With Riboflavin Solution for Previously Untreated Corneal Ulcers

Corneal Ulcer Clinical Trial

Official title:

Safety and Effectiveness of the PXL Platinum 330 System With Riboflavin Solution for Previously Untreated Corneal Ulcers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05255107
• Other study ID #: PXL-330-02B
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 14, 2022
• Est. completion date: February 24, 2024

Study information

• Verified date: July 2022
• Source: Peschke GmbH
• Contact: Patricia Huezo-Diaz Curtis, PhD
• Phone: 0041 (0) 787 422151
• Email: Patricia.Huezo-Diaz[@]confinis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being conducted to evaluate the safety and effectiveness of using the PXL Platinum 330 System with riboflavin solution for performing corneal collagen crosslinking (CXL) for the treatment of previously untreated corneal ulcers. The PXL Platinum 330 System is a combination product consisting of an ultraviolet A (UV-A) 365 nm wavelength light source (PXL Platinum 330 Illumination System) and riboflavin (Riboflavin 0.23% PESCHKE-L Solution) administered in conjunction with the UV-A light as a photosensitizer. The PXL Platinum 330 System is intended to induce corneal collagen CXL to improve the biomechanical properties of the cornea by strengthening the corneal tissue in the anterior stroma. Corneal collagen CXL is performed by pretreating the cornea with riboflavin ophthalmic solution beginning 40 min before UV-A light exposure to saturate the corneal tissue with the riboflavin photosensitizer. The cornea is then irradiated with UV-A light (365 nm) at an irradiance of 18 mW/cm2 (5 seconds on, 5 seconds off) for 10 min. Exposure of the cornea to this UV-A light regimen after topical administration of riboflavin ophthalmic solution has been shown to induce CXL of the corneal collagen fibrils, with a resultant increase in tensile strength and diameter of the collagen fibrils. Clinically, CXL has been shown to stabilize the corneal curvature in eyes with progressive keratoconus, with no significant change in the refractive index of the cornea. Numerous reports and a few clinical trials have also shown benefit in aiding resolution of infective corneal ulcers.

Description:

This is a prospective, 2-arm parallel-group, single-masked, randomized multicenter study to determine the safety and effectiveness of the PXL Platinum 330 System for performing CXL in eyes with previously untreated corneal ulcers. Subjects with documented infectious corneal ulcers that have not been treated (treatment na ve) will be evaluated initially for suitability as candidates for CXL. Subjects who are candidates for CXL will be asked to participate in this study and will undergo the required screening procedures to determine study eligibility. Informed consent will be obtained from each subject before performance of any required study procedures that are not part of the investigator's routine examination. After completing screening procedures, the diagnosis for each eligible eye will be confirmed. Subjects will be randomized to 1 of 2 groups, both including standard of care (SOC) treatment:

1. SOC: Moxifloxacin 0.5% eyedrop therapy every 1 hour (q1h) while awake; to be tapered at treating physician's discretion

2. CXL + SOC: Moxifloxacin 0.5% eyedrop therapy + CXL

Eyes undergoing CXL will have topical anesthetic administered and then have topical riboflavin instilled onto the cornea every 2 min (or longer as needed to assure adequate corneal penetration), after which the cornea will be exposed to UV-A pulsed light 18 mW/cm2 for 10 min. Riboflavin instillation will continue every 2 min during CXL. The CXL procedures will be performed on an outpatient basis using the PXL Platinum 330 System (UV-A light source and riboflavin solution). All use of the PXL Platinum 330 System will be in accordance with this protocol and the general instructions provided by the manufacturer (PESCHKE) in the PXL Platinum 330 Illumination System Operator's Manual. All subjects will be evaluated at Screening/Baseline, Day 0 (Randomization/Treatment), Day 1, Day 3 ( 1 day), Week 1 ( 2 days), Week 2 ( 2 days), and Week 4 ( 3 days) after treatment. Efficacy monitoring throughout the study will include observations at appropriate times for re-epithelialization, size of infection, and corneal culture results. Safety monitoring throughout the study will include observations at appropriate times for pain, IOP, BSCVA, corneal scar size, AEs, clinically significant findings on ophthalmic examination, dilated fundus examination, and slit lamp examination. After treatment, subjects will be followed at the treating physician's discretion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 468
• Est. completion date: February 24, 2024
• Est. primary completion date: November 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects who have one or both eyes that meet the following criteria will be considered candidates for this study:

1. 18 years of age or older

2. Ulcers that have not been treated with ophthalmic antibiotic eyedrops (eg, quinolone, polymyxin/trimethoprim, erythromycin, vancomycin, tobramycin, cefazolin, or other ophthalmic antimicrobials) in the preceding 30 days erythromycin, vancomycin, tobramycin, cefazolin, or other ophthalmic antimicrobials) in the preceding 30 days

3. Consent to a corneal culture for suspected bacterial keratitis (defined as a corneal epithelial defect of any size with an infiltration of the underlying stroma)

4. Signed written informed consent

5. Willingness and ability to comply with schedule for follow-up visits

6. Minimum corneal thickness >300 µm

Exclusion Criteria:

• All subjects meeting any of the following criteria will be excluded from this study:

1. Presence of a perforated corneal ulcer

2. Presence of a corneal ulcer that had produced a descemetocele

3. Presence of a corneal ulcer deeper than 50% depth or 275 µm in the cornea

4. Any active ocular infection other than the corneal ulcer to be treated

5. Suspicion of amoebic or viral keratitis requiring treatment with topical anti-amoebic or topical antiviral ophthalmic medications

6. Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye(s) for future complications. This may include history of or active corneal disease (eg, herpes simplex, herpes zoster keratitis, recurrent erosion syndrome, acanthamoeba, etc.)

7. Uncontrolled systemic disease, especially a collagen-vascular or rheumatologic condition that could be contributing to the corneal condition

8. Pregnancy (or plan to become pregnant) or lactation during the course of the study

9. A known sensitivity to study medications

10. Presence of nystagmus or any other condition that would prevent a steady gaze during the CXL treatment or other diagnostic tests

Related Conditions & MeSH terms

• Corneal Ulcer
• Keratitis
• Ulcer

Intervention

Combination Product:
• Standard of Care Therapy + CXL + Riboflavin 0.23% L Solution
Standard Of Care: Moxifloxacin 0.5% eyedrop therapy every 1 hour (q1h) while awake; to be tapered at treating physician's discretion. Following SOC, for subjects randomized to the experimental arm, riboflavin will be administered (1 drop every 2 min for 40 min with PESCHKE-L solution [0.23%], or longer as needed to assure adequate corneal penetration). Then the eye will be aligned under the PXL Platinum 330 light (the treatment plane will be at the correct working distance from the PXL Platinum 330 beam aperture when the border of the projected beam is in sharp focus). The correct aperture setting (3 to 12 mm) will be selected for the size of the eye and area needing to be treated (2 mm larger than the maximal ulcer diameter), and the eye will be irradiated at 18 mW/cm2, with pulsed mode (5 seconds on, 5 seconds off) for 10 min, during which time instillation of riboflavin will continue (1 drop every 2 min).

Other:
• Standard of Care Therapy + Sham CXL + Artificial Tears
Standard Of Care: Moxifloxacin 0.5% eyedrop therapy every 1 hour (q1h) while awake; to be tapered at treating physician's discretion. Following SOC, for subjects randomized to the Sham comparator group, artificial tears (1 drop every 2 min for 40 min) will be administered. After instillation of artificial tears, the eye will be aligned under the PXL Platinum 330 light. The instrument will be kept off and the subject will be kept under the device for 10 min, during which time instillation of artificial tears will be performed (1 drop every 2 min) to maintain corneal hydration. The operator will keep track of sham exposure time independently to confirm the actual duration.

Locations

Country	Name	City	State
United States	SightMD	Babylon	New York
United States	Woolfson Eye	Chattanooga	Tennessee
United States	Prisma Health Opthalmology	Columbia	South Carolina
United States	Gorovoy M.D Eye Specialists	Fort Myers	Florida
United States	Houston Eye Associates	Houston	Texas
United States	Price Vision Group	Indianapolis	Indiana
United States	San Antonio Eye Center	Lackland Air Force Base	Texas
United States	Colorado Eye Consultants	Littleton	Colorado
United States	Milwaukee Eye Surgeons	Milwaukee	Wisconsin
United States	Valley Eye	Oshkosh	Wisconsin
United States	Bay Area Eye Institute	Tampa	Florida
United States	The cornea & Laser Eye Institute-NJ	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Peschke GmbH

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety and effectiveness of corneal collagen CXL for treating previously untreated corneal ulcers	Primary Outcome Measure: The composite primary endpoint outcome would be the proportion of patients in the treated group, compared to the control group, who achieve all three of the following components: complete re-epithelialization at week 2, defined as absence of corneal fluorescein staining noted with the blue light of the slit lamp by the investigator.; no expansion of infiltrate from baseline to week 2. The size of the infiltrate will be reviewed by the investigator using the slit lamp exam and compared to baseline measures to assess expansion of the infiltrate.; a negative corneal culture at week 2; Each of the components of this composite endpoints is a binary outcome (yes or no), and are NOT measured as units of measure.	Week 2 (#+/- 2 study days).