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

NCT ID: NCT05255016

Last Updated: 2022-10-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 488 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-14
• Study Completion Date: 2024-02-24

Brief 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 refractory 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 (Peschke Riboflavin 0.25% Transepithelial 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 0.25% 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 (0.25%) 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.

Detailed Description

This is a prospective, 2-arm parallel-group, single-blind, randomized multicenter study to determine the safety and effectiveness of the PXL Platinum 330 System for performing CXL in eyes with refractory corneal ulcers. Subjects with a history of non-resolving infective corneal ulcers will be evaluated initially for suitability as a candidate 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:

1. Group 1: Standard-of-care therapy (anti fungal drops if there is clinical suspicion for fungus, fortified antibiotics if corneal culture is positive for a specific organism sensitive to a fortified antibiotic, and empiric antibiotic drops based on community prevalence if corneal culture is negative and there is no clinical suspicion for fungus)

2. Group 2: Standard-of-care 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), Week 4 ( +/- 3 days), and Week 6 ( +/- 4 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.

Conditions

Keratitis; Corneal Ulcer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard of care + Sham CXL + Artificial Tears

Standard-of-care treatment and Sham CXL and administration of artificial tears.

Group Type: SHAM_COMPARATOR

Sham CXL + Artificial Tears

Intervention Type: OTHER

Standard-of-care therapy (antifungal drops or fortified antibiotics and empiric antibiotic drops). In addition, for subjects in the sham 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.

Standard of care + CXL + Riboflavin 0.25% TE Solution

Standard of care treatment and the experimental combination product. The PXL Platinum 330 Illumination System is a portable electronic medical device. The device's light emitting diode (LED) is used to deliver a metered dose of UV-A light to a targeted treatment area for illuminating the cornea during corneal collagen CXL. The riboflavin solution is an isotonic (0.9%) sodium chloride solution containing 0.25% riboflavin, 1% hydroxypropylmethylcellulose, and 0.007% benzalkonium chloride, adjusted to a pH of 7.0, and packaged in 2 mL sterile syringes for topical ophthalmic use.

Group Type: EXPERIMENTAL

PXL Platinum 330 system + Riboflavin 0.25% TE Solution

Intervention Type: COMBINATION_PRODUCT

Standard-of-care therapy (antifungal drops or fortified antibiotics and empiric antibiotic drops). In addition CXL + Riboflavin 0.25% TE solution.

After topical anesthesia, the surgeon or trained designee will apply topical riboflavin (1 drop every 2 min for 40 min with PESCHKE TE solution [0.25%], or longer as needed to assure adequate corneal penetration). At the end of this pre-treatment period, the eye will be examined at the slit lamp with the blue filter for the presence of riboflavin throughout the stroma. When sufficient corneal riboflavin penetration is confirmed, the eye will be aligned under the PXL Platinum 330 light. 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).

Interventions

PXL Platinum 330 system + Riboflavin 0.25% TE Solution

Standard-of-care therapy (antifungal drops or fortified antibiotics and empiric antibiotic drops). In addition CXL + Riboflavin 0.25% TE solution.

After topical anesthesia, the surgeon or trained designee will apply topical riboflavin (1 drop every 2 min for 40 min with PESCHKE TE solution [0.25%], or longer as needed to assure adequate corneal penetration). At the end of this pre-treatment period, the eye will be examined at the slit lamp with the blue filter for the presence of riboflavin throughout the stroma. When sufficient corneal riboflavin penetration is confirmed, the eye will be aligned under the PXL Platinum 330 light. 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).

Intervention Type: COMBINATION_PRODUCT

Sham CXL + Artificial Tears

Standard-of-care therapy (antifungal drops or fortified antibiotics and empiric antibiotic drops). In addition, for subjects in the sham 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.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. 18 years of age or older

2. Central corneal ulcer or hypopyon, and/or failure to improve within 24 hours of initiating conventional antibiotic eyedrops (eg, quinolone, polymyxin/trimethoprim, erythromycin, or other non-fortified antibiotics) or failure to completely re-epithelialisation within 1 week of initiating conventional antibiotic drops

3. Consent to a corneal culture for bacterial keratitis (suspected keratitis is 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

1. Presence of a perforated corneal ulcer

2. Presence of a corneal ulcer that has 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 central corneal ulcer or hypopyon 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 contribute 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peschke GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvette Viscuso

Role: STUDY_DIRECTOR

Peschke GmbH

Bala Ambati

Role: PRINCIPAL_INVESTIGATOR

Pacific Clear Vision Institute

Locations

Colorado Eye Consultants

Littleton, Colorado, United States

Site Status: RECRUITING

Gorovoy M.D Eye Specialists

Fort Myers, Florida, United States

Site Status: RECRUITING

Bay Area Eye Institute

Tampa, Florida, United States

Site Status: RECRUITING

Price Vision Group

Indianapolis, Indiana, United States

Site Status: RECRUITING

The cornea & Laser Eye Institute-NJ

Teaneck, New Jersey, United States

Site Status: RECRUITING

SightMD

Babylon, New York, United States

Site Status: RECRUITING

Prisma Health Opthalmology

Columbia, South Carolina, United States

Site Status: RECRUITING

Woolfson Eye

Chattanooga, Tennessee, United States

Site Status: RECRUITING

Houston Eye Associates

Houston, Texas, United States

Site Status: RECRUITING

San Antonio Eye Center

Lackland Air Force Base, Texas, United States

Site Status: RECRUITING

Milwaukee Eye Surgeons

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Valley Eye

Oshkosh, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Patricia Huezo-Diaz Curtis, PhD

Role: CONTACT

Patricia.Huezo-Diaz@confinis.com

0041 (0) 787 422151

Elizabeth Hernandez, Bs

Role: CONTACT

elizabethhernandez@trialrunners.com

+1(701) 300-3702

Facility Contacts

Lance Forstot, MD

Role: primary

Mark Gorovoy, MD

Role: primary

Craig Berger, MD

Role: primary

Francis Price, MD

Role: primary

Peter Hersh, MD

Role: primary

Eric Rosenberg, MD

Role: primary

Shawn Iverson, MD

Role: primary

Jonathan Woolfson, MD

Role: primary

John Goosey, MD

Role: primary

Vasudha Panday, MD

Role: primary

Ken Weinlander

Role: primary

Michael Vrabec, MD

Role: primary

Other Identifiers

PXL-330-02A

Identifier Type: -

Identifier Source: org_study_id