NCT05457647: ARGO

Theranostic Guided Riboflavin/UV-A Corneal Cross-linking

Completed NA Results posted Last updated 11 February 2025

What this trial tests

NA trial testing Riboflavin/UV-A corneal cross-linking in Keratoconus in 50 participants. Completed in 26 January 2024.

Timeline

27 April 2022

Primary endpoint
26 January 2024

26 January 2024

Quick facts

Lead sponsor	Regensight
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	50
Start date	27 April 2022
Primary completion	26 January 2024
Estimated completion	26 January 2024
Sites	3 locations across Italy

Drugs / interventions tested

• Riboflavin/UV-A corneal cross-linking

Conditions studied

• Keratoconus — all drugs for Keratoconus →

Sponsor

Regensight

Who can join

Adults 18 to 40, any sex, with Keratoconus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Validation of the Theranostic Scores Primary · 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.

Accuracy

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	91	79 – 98

Precision

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	95	89 – 99

Corneal Topography Secondary · 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.

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-1.5	± 1.6

Endothelial Cell Density Secondary · 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.

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-63	± 336

Manifest Refraction Secondary · 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.

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	0.2	± 1.2

Corrected Distance Visual Acuity Secondary · 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.

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-0.1	± 0.1

Uncorrected Distance Visual Acuity Secondary · 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.

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-0.1	± 0.1

Central Corneal Thickness Secondary · 12 months

Change of Central Corneal Thickness (CCT). This outcome was assessed by measuring changes of CCT from baseline to 12 months postoperatively.

Group	Value	95% CI
Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-5	± 18

Stratification Groups Secondary · 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.

Group	Value	95% CI
Epi-off Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-1.9	± 2.0
Epi-on Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module	-1.1	± 1.0

Adverse events — posted to ClinicalTrials.gov

Time frame: 1-week, 1-month, 3-months, 6-months and 12-months,.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Riboflavin/UV-A Corneal Cross-linking Monitored by Theranostic Software Module

Serious: 0/50 (0%)

Deaths: 0/50

Other adverse events (1 terms — click to expand)

Reaction	System	Riboflavin/UV-A Corneal Cr…
Corneal Haze	Eye disorders	—

Data from ClinicalTrials.gov NCT05457647 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. A randomized clinical trial assessing theranostic-guided corneal cross-linking for treating keratoconus: the ARGO protocol.
   Roszkowska AM, Lombardo G, Mencucci R, Scorcia V, et al · · 2023 · cited 8× · PMID 36587174 · DOI 10.1007/s10792-022-02628-4
2. Assessment of the Predictive Ability of Theranostics for Corneal Cross-linking in Treating Keratoconus: A Randomized Clinical Trial.
   Roszkowska AM, Scorcia V, Mencucci R, Giannaccare G, et al · · 2024 · cited 5× · PMID 38908553 · DOI 10.1016/j.ophtha.2024.06.012