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KeratoconusARGONCT05457647

Theranostic Guided Riboflavin/UV-A Corneal Cross-linking

A study testing Riboflavin/UV-A corneal cross-linking in people with Keratoconus, run by Regensight at 3 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 40 years
Conditions the study is for
Keratoconus
What is being tested?
Riboflavin/UV-A corneal cross-linking
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
3 sitesItaly
Study dates
27 Apr 2022to 26 Jan 2024
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 40 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • Anterior corneal curvature steeper than 63 D;
  • Corneal thickness thinner than 400 µm;
  • Corneal scarring;
  • Descemetocele;
  • History of herpetic keratitis;
  • Concomitant eye diseases;
Show all 12Show fewer
  • Inflammatory eye diseases;
  • Glaucoma;
  • Cataract;
  • Nistagmus;
  • Pregnancy;
  • Breast feeding.

Trial locations and contacts

3 sites in 1 country.

Italy3 sites
  • Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro

    Catanzaro, 88100

  • Azienda Ospedaliera Universitaria Careggi, Università di Firenze

    Florence, 50134

  • Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina

    Messina, 98124

Other trials in Italy

About this study

Official title: 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.

Read the 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.

Conditions
Keratoconus
Being tested
Riboflavin/UV-A corneal cross-linking
Keywords
theranostics, riboflavin, UV-A light, corneal cross-linking
Medical subject headings
Keratoconus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Riboflavin/UV-A corneal cross-linkingDevice

    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.

Study groups in NCT05457647
Study groupRoleWhat they receive
Riboflavin/UV-A corneal cross-linking monitored by theranostic software moduleExperimentalOne 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.
Receives: Device: Riboflavin/UV-A corneal cross-linking

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Validation of the Theranostic Scores

    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.

    Measured: 12 months

Secondary outcomes (2)
  1. Corneal Topography

    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.

    Measured: 12 months

  2. Endothelial Cell Density

    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.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2022
  2. Study start27 Apr 2022
  3. Primary completion26 Jan 2024
  4. Study completion26 Jan 2024

Resources

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 N/A
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Model description
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. If both eyes of a study participant are eligible, the eye with worst CDVA is enrolled and treated.
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05457647
Sponsor's protocol ID
RSKC001
Acronym
ARGO
Status last verified
Feb 2025
First submitted
11 Jul 2022
Last updated
11 Feb 2025
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Lombardo G, Villari V, Micali NL, Leone N, Labate C, De Santo MP, Lombardo M. Non-invasive optical method for real-time assessment of intracorneal riboflavin concentration and efficacy of corneal cross-linking. J Biophotonics. 2018 Jul;11(7):e201800028. doi: 10.1002/jbio.201800028. Epub 2018 Apr 10.

    PubMed 29451741
  • Lombardo M, Lombardo G. Noninvasive real-time assessment of riboflavin consumption in standard and accelerated corneal crosslinking. J Cataract Refract Surg. 2019 Jan;45(1):80-86. doi: 10.1016/j.jcrs.2018.07.062. Epub 2018 Oct 22.

    PubMed 30360937
  • Lombardo G, Serrao S, Lombardo M. Comparison between standard and transepithelial corneal crosslinking using a theranostic UV-A device. Graefes Arch Clin Exp Ophthalmol. 2020 Apr;258(4):829-834. doi: 10.1007/s00417-019-04595-6. Epub 2020 Jan 3.

    PubMed 31900647
  • Lombardo G, Micali NL, Villari V, Serrao S, Lombardo M. All-Optical Method to Assess Stromal Concentration of Riboflavin in Conventional and Accelerated UV-A Irradiation of the Human Cornea. Invest Ophthalmol Vis Sci. 2016 Feb;57(2):476-83. doi: 10.1167/iovs.15-18651.

    PubMed 26868750
  • Lombardo M, Pucci G, Barberi R, Lombardo G. Interaction of ultraviolet light with the cornea: clinical implications for corneal crosslinking. J Cataract Refract Surg. 2015 Feb;41(2):446-59. doi: 10.1016/j.jcrs.2014.12.013. Epub 2014 Dec 23.

    PubMed 25542349
  • Lombardo G, Bernava GM, Serrao S, Lombardo M. Theranostic-guided corneal cross-linking: Preclinical evidence on a new treatment paradigm for keratoconus. J Biophotonics. 2022 Dec;15(12):e202200218. doi: 10.1002/jbio.202200218. Epub 2022 Sep 16.

    PubMed 36059083
  • Roszkowska AM, Lombardo G, Mencucci R, Scorcia V, Giannaccare G, Vestri A, Alunni Fegatelli D, Bernava GM, Serrao S, Lombardo M. A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol. Int Ophthalmol. 2023 Jul;43(7):2315-2328. doi: 10.1007/s10792-022-02628-4. Epub 2022 Dec 31.

    PubMed 36587174
  • Roszkowska AM, Scorcia V, Mencucci R, Giannaccare G, Lombardo G, Alunni Fegatelli D, Vestri A, Bifezzi L, Bernava GM, Serrao S, Lombardo M. Assessment of the Predictive Ability of Theranostics for Corneal Cross-linking in Treating Keratoconus: A Randomized Clinical Trial. Ophthalmology. 2024 Dec;131(12):1403-1415. doi: 10.1016/j.ophtha.2024.06.012. Epub 2024 Jun 20.

    PubMed 38908553

Questions about this trial

What is this clinical trial studying?

A study testing Riboflavin/UV-A corneal cross-linking in people with Keratoconus, run by Regensight at 3 sites in Italy.

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 4 inclusion and 12 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: finished, as of the sponsor's last update on 11 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Italy. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Validation of the Theranostic Scores (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05457647, which also lists 8 linked publications.

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 11 Feb 2025.

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