Clinical trial NCT05457647: Theranostic Guided Riboflavin/UV-A Corneal Cross-linking
Official title: Assessment of Theranostic Guided Riboflavin/UV-A Corneal Cross-linking for Treatment of Keratoconus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Keratoconus
Keywords: theranostics
riboflavin
UV-A light
corneal cross-linking
Lead sponsor: Regensight
Sponsor class: INDUSTRY
Collaborators: name: University of Roma La Sapienza
First posted: 2022-07-14
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: OTHER

Brief 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. 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Validation of the Theranostic Scores
timeFrame: 12 months
Secondary outcomes:
measure: Corneal Topography
timeFrame: 12 months
measure: Endothelial Cell Density
timeFrame: 12 months
Other outcomes:
measure: Manifest Refraction
timeFrame: 12 months
measure: Corrected Distance Visual Acuity
timeFrame: 12 months
measure: Uncorrected Distance Visual Acuity
timeFrame: 12 months
measure: Central Corneal Thickness
timeFrame: 12 months
measure: Stratification Groups
timeFrame: 12 months
Locations:
city: Catanzaro
country: Italy
facility: Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi, Università di Firenze
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina
Study officials:
affiliation: Azienda Ospedaliera Universitaria Mater Domini - Università Magna Graecia di Catanzaro
name: Vincenzo Scorcia, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Studio Italiano di Oftalmologia
name: Marco Lombardo, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.