Theranostic Guided Riboflavin/UV-A Corneal Cross-linking (ARGO)

February 10, 2025 updated by: Regensight

Assessment of Theranostic Guided Riboflavin/UV-A Corneal Cross-linking for Treatment of Keratoconus

This is a clinical study consisting of a study arm to validate accuracy and precision of the combined use of theranostic imaging biomarkers, riboflavin score and theranostic score, to assess and predict efficacy of corneal cross-linking in flattening the corneal topography Kmax value at 12-months postoperatively. The objective of the study is to assess the performance of the theranostic software module (Research Use Only) of a CE marked (CE1936) UV-A medical device, C4V CHROMO4VIS™, in order to validate its use for theranostic-guided corneal cross-linking treatment of keratoconus and corneal ectasia. The study hypothesis is that theranostic-guided riboflavin/UV-A corneal cross-linking with the C4V CHROMO4VIS™ system is safe and can estimate treatment efficacy during operation, regardless of treatment protocol, i.e., either with or without epithelial removal.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Keratoconus is a naturally-occurring ocular condition characterized by progressive thinning and steepening of the central cornea, resulting in corneal optical irregularities with increasing myopia, irregular astigmatism, corneal opacity and consequential loss of visual acuity. Riboflavin/UV-A corneal cross-linking is a procedure used to biomechanically stabilize the weak cornea in keratoconus and to slow down or halt the clinical progression of this disease. Theranostics is an emerging therapeutic paradigm that enables monitoring of image-guided therapy through the use of a theranostic module that makes use of real-time non-invasive molecular imaging analysis of the tissue being treated to achieve optimal treatment outcomes in the management of disease on a personal basis.

The theranostic software module of the C4V CHROMO4VIS™ medical device is able to measure the concentration of riboflavin into the cornea during treatment (i.e., the riboflavin score) and to provide the surgeon with an objective assessment of treatment efficacy (i.e., the theranostic score).

The scope of this study is to validate the combined use of the theranostic imaging biomarkers in predicting the flattening of corneal topography Kmax value at 1-year postoperatively. The 1-year follow-up is long enough to provide scientific evidence of the safety and efficacy of the theranostic UV-A medical device in question. A pre-operative examination ensures that every interested and willing participant fulfils the inclusion criteria of this study. Masked post-operative examinations are carried out after 1 week, 1 month, 3 months, 6 months and 12 months.

This is a multi-center clinical trial. Eligible participants are stratified with allocation ratio 1:1 into either treatment protocol (epi-off CXL and epi-on CXL) using a computer-generated stratification plan with blocks. Two different blocks are created, which include eyes with Kmax steeper or flatter than 54.0 D to allocate patients with comparable baseline Kmax values in either treatment protocol.

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Catanzaro, Italy, 88100
        • Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro
      • Firenze, Italy, 50134
        • Azienda Ospedaliera Universitaria Careggi, Università di Firenze
      • Messina, Italy, 98124
        • Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

criteria for inclusion in the clinical trial are those currently referred to as the golden standard for the treatment of corneal cross-linking. The criterion to determine progression of keratoconus is based on providing at least one of the following evidences:

  • at least two Placido disk corneal topography measurements showing at least +1.00 D steepening of the Kmax value in the last year or longer interval period.
  • at least two manifest refraction measurements showing at least -0.50 D change in spherical equivalent refraction in the last year or longer interval period.
  • at least two central corneal thickness (CCT) measurements showing at least -10 µm change in in the last year or longer interval period.

Exclusion Criteria:

  • Anterior corneal curvature steeper than 63 D;
  • Corneal thickness thinner than 400 µm;
  • Corneal scarring;
  • Descemetocele;
  • History of herpetic keratitis;
  • Concomitant eye diseases;
  • Inflammatory eye diseases;
  • Glaucoma;
  • Cataract;
  • Nistagmus;
  • Pregnancy;
  • Breast feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Riboflavin/UV-A corneal cross-linking monitored by theranostic software module
One study arm receiving riboflavin/UV-A corneal cross-linking with either standard, epi-off, or transepithelial, epi-on, treatment protocol. Only one eye of each participant is designated as the study eye.
Device: Riboflavin/UV-A corneal cross-linking
Corneal cross-linking procedure is performed using the C4V CHROMO4VIS™ medical device equipped with theranostic software module in all participants. Participants will receive a single dose of the 0.22% riboflavin ophthalmic solution, RitSight™. Application of the riboflavin eye drop is done for 15 minutes for the epi-off CXL treatment and 20 minutes for the epi-on CXL treatment. Estimates of riboflavin concentration into the cornea are monitored by the C4V CHROMO4VIS™ system during the dosing phase of treatment. Once the pre-set dosing phase is completed, the C4V CHROMO4VIS™ system provides the Operator the access to the UV-A light irradiation of the cornea with 5.4 J/cm2 total energy dose (10 mW/cm2 for 9 min.) and 7.00 mm light beam diameter in all participants. Estimates of treatment efficacy by calculation of theranostic score are performed by the C4V CHROMO4VIS™ system during UV-A light irradiation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Validation of the Theranostic Scores
Time Frame: 12 months

The aim of this study is to validate the combined use of theranostic imaging biomarkers in predicting the propsensity of corneal corneal cross-linking (CXL) in flattening the Kmax at 1-year.

The accuracy and precision (95% CI) of the combined use of the theranostic imaging biomarkers to predict CXL treatment outcome are determined by calculating the percentage of correctly classified eyes and the positive predictive value (PPV) respectively.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Corneal Topography
Time Frame: 12 months
Change of Maximum Keratometry value of Placido disc corneal topography. The secondary outcome measure of efficacy was assessed by measuring changes of Kmax value (D) from baseline to 12 months postoperatively.
12 months
Endothelial Cell Density
Time Frame: 12 months
Change of Endothelial Cell Density (ECD) of the cornea. The secondary outcome measure of safety was assessed by measuring change of ECD (cell/mm^2) from baseline to 12 months postoperatively.
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Manifest Refraction
Time Frame: 12 months
Change of Manifest Spherical Equivalent Refraction (MSER). This outcome was assessed by measuring change of MSER (D) from baseline to 12 months postoperatively.
12 months
Corrected Distance Visual Acuity
Time Frame: 12 months

Change of Corrected Distance Visual Acuity (CDVA) measured with ETDRS chart and expressed in LogMAR.

This outcome was assessed by measuring changes of CDVA from baseline to 12 months postoperatively.

A negative change means improvement in CDVA after treatment.
12 months
Uncorrected Distance Visual Acuity
Time Frame: 12 months

Change of Uncorrected Distance Visual Acuity (UDVA) measured with ETDRS chart and expressed in LogMAR.

This outcome was assessed by measuring changes of UDVA from baseline to 12 months postoperatively.

A negative change means improvement in UDVA after treatment.
12 months
Central Corneal Thickness
Time Frame: 12 months
Change of Central Corneal Thickness (CCT). This outcome was assessed by measuring changes of CCT from baseline to 12 months postoperatively.
12 months
Stratification Groups
Time Frame: 12 months

Change of primary and secondary outcome measures in either stratification group (epi-off CXL protocol and epi-on CXL protocol).

These exploratory outcome measures included the following assessment: assessmentg of changes of Kmax value (D) at 12-months postoperatively in either stratification group.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Regensight

Collaborators

University of Roma La Sapienza

Investigators

  • Principal Investigator: Vincenzo Scorcia, MD, Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro
  • Study Director: Marco Lombardo, MD, PhD, Studio Italiano di Oftalmologia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 27, 2022

Primary Completion (Actual)

January 26, 2024

Study Completion (Actual)

January 26, 2024

Study Registration Dates

First Submitted

July 11, 2022

First Submitted That Met QC Criteria

July 11, 2022

First Posted (Actual)

July 14, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 10, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RSKC001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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