KeratoconusPhase 2NCT03029104

Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas

A Phase 2 study testing CXLO Corneal Strengthening Solution and UVA Illumination Device in people with Keratoconus and Corneal Diseases, run by Cxlusa at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial summary

This study will assess changes in visual acuity and corneal symmetry after corneal collagen cross-linking (CXL) of asymmetric corneas. Read more about this study

Who is it for?: Ages 8 years and older
Conditions the study is for: Keratoconus, Corneal Diseases, Eye Diseases
What is being tested?: CXLO Corneal Strengthening Solution and UVA Illumination Device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2,228 participants
Where: 9 sitesUnited States
Study dates: 21 Dec 2016to 27 Dec 2020
Phase: Phase 2
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 8 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

A diagnosis of at least one of the following conditions:
Keratoconus
Forme fruste keratoconus
Post-LASIK ectasia
Pellucid marginal degeneration
Forme fruste pellucid marginal degeneration
Diurnal fluctuation post-radial keratotomy
Terrien's marginal degeneration

Who cannot join

Corneal thickness < 375 microns measured by ultrasound or Pentacam.
Contraindications or hypersensitivities to any study medications or their components.
Pregnancy or breastfeeding.
Any history of herpes simplex corneal disease in an eye to be treated.
Nystagmus or any other condition that would, in the judgement of the investigator, prevent a steady gaze during the treatment.
Inability to cooperate with diagnostic tests.
Enrollment in another ophthalmic clinical trial.

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

Woolfson Eye Institute
Atlanta, Georgia, 30328
Cleveland Eye Clinic
Brecksville, Ohio, 44141
Chicago Cornea Consultants
Chicago, Illinois, 60035
Cornea Associates of Texas
Dallas, Texas, 75231
Chicago Cornea Consultants, Ltd.
Hoffman Estates, Illinois, 60169
Cornea Consultants of Colorado
Littleton, Colorado, 80120-4508
Goodman Eye Center
San Francisco, California, 94115
Schwartz Laser Eye Center
Scottsdale, Arizona, 85260
Ophthalmology Associates
St Louis, Missouri, 63110

Other trials in United States

About this study

This study will assess changes in visual acuity and corneal symmetry after corneal collagen cross-linking (CXL) of asymmetric corneas.

Read the detailed description

This study will evaluate the results of Corneal Collagen Crosslinking (CXL) in patients with conditions that include keratoconus, forme fruste keratoconus, post-LASIK ectasia, pellucid marginal degeneration, forme fruste pellucid marginal degeneration, diurnal fluctuation post-radial keratotomy, or Terrien's marginal degeneration. This is an outcomes study, all patients receive treatment.

Conditions: Keratoconus, Corneal Diseases, Eye Diseases, Photosensitizing Agents
Being tested: CXLO Corneal Strengthening Solution and UVA Illumination Device
Keywords: Keratoconus, Forme fruste keratoconus, Post-LASIK ectasia, Pellucid marginal degeneration, Forme fruste pellucid marginal degeneration, Diurnal fluctuation post-radial keratotomy, Terrien's marginal degeneration
Medical subject headings: Keratoconus, Corneal Diseases, Eye Diseases

What participants receive

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

CXLO Corneal Strengthening Solution and UVA Illumination DeviceCombination product
CXLO Corneal Strengthening Solution

Study groups in NCT03029104
Study group	Role	What they receive
Group 1	Active comparator	Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes. Receives: Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination Device
Group 2	Active comparator	Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes. Receives: Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination Device
Group 3	Active comparator	Ultraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes. Receives: Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination Device

What is being measured

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

Change From Baseline in Corrected Distance Visual Acuity (CDVA)
Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline
Measured: Baseline and 6 and 12 months

Secondary outcomes (2)

Change From Baseline in Uncorrected Distance Visual Acuity (UCVA)
Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline
Measured: Baseline and 6 and 12 months
Change From Baseline in Maximum Keratometry (KMax)
Kmax is the maximum value of corneal curvature in Diopters. Changes in Kmax are reported as the value at 6 and 12 months minus the value at baseline.
Measured: Baseline and 6 and 12 months

Timeline

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

21 Dec 201627 Dec 2020

First posted24 Jan 2017 (estimated)
Study start21 Dec 2016
Primary completion27 Dec 2020
Study completion27 Dec 2020

Why it stopped: Sufficient clinical results obtained to support study endpoints.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for KeratoconusStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 2,228 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03029104
Sponsor's protocol ID: CXL-005
Status last verified: Dec 2021
First submitted: 20 Jan 2017
Last updated: 12 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No

Publications

Epstein RJ, Belin MW, Gravemann D, Littner R, Rubinfeld RS. EpiSmart Crosslinking for Keratoconus: A Phase 2 Study. Cornea. 2023 Jul 1;42(7):858-866. doi: 10.1097/ICO.0000000000003136. Epub 2022 Sep 28.
PubMed 36173242

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
UNITY DX Cornea Study
Tomography
Not yet recruiting
Performance Evaluation of the OCUTOP Hand-held Corneal Topographer
Corneal Topography, Dry Eye Syndromes
Recruiting
Proof-of-Concept for a Novel Optical Aperture Contact Lens in Presbyopia and Keratoconus
Keratoconus, Presbyopia
RecruitingObservational study
A Study to Test the Diagnostic Potential of Brillouin Microscopy for Corneal Ectasia
Keratoconus, Ectasia
Enrolling by invitationObservational study
Corneal Biomechanical Analysis Using Brillouin Microscopy
Keratoconus, Keratoconus, Unstable

All Keratoconus trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas
ClinicalTrials.gov ID: NCT03029104
Acronym / sponsor ID: CXL-005
Conditions: Keratoconus, Corneal Diseases, Eye Diseases, Photosensitizing Agents
Keywords: Keratoconus, Forme fruste keratoconus, Post-LASIK ectasia, Pellucid marginal degeneration, Forme fruste pellucid marginal degeneration, Diurnal fluctuation post-radial keratotomy, Terrien's marginal degeneration
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sufficient clinical results obtained to support study endpoints.
Enrolment: 2,228 participants (actual)
Lead sponsor: CxlusaIndustry (pharma, biotech, devices)
Study start: 21 Dec 2016 (actual)
Primary completion: 27 Dec 2020 (actual)
Study completion: 27 Dec 2020 (actual)
First posted: 24 Jan 2017 (estimated)
Results: Posted 12 Jan 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study will assess changes in visual acuity and corneal symmetry after corneal collagen cross-linking (CXL) of asymmetric corneas.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Group 1	Active comparator	Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination DeviceUltraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.
Group 2	Active comparator	Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination DeviceUltraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 6 mW/cm2 cycled On/Off at 15 second intervals for 20 minutes.
Group 3	Active comparator	Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination DeviceUltraviolet-A (UVA)-induced cross-linking of corneal collagen (CXL) using CXLO Corneal Strengthening Solution and a UVA irradiance of 4 mW/cm2 cycled On/Off at 15 second intervals for 30 minutes.

Who may qualify

Ages: 8 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (8 listed)

A diagnosis of at least one of the following conditions:

Key exclusion criteria (7 listed)

Corneal thickness < 375 microns measured by ultrasound or Pentacam.
Contraindications or hypersensitivities to any study medications or their components.
Pregnancy or breastfeeding.
Any history of herpes simplex corneal disease in an eye to be treated.
Nystagmus or any other condition that would, in the judgement of the investigator, prevent a steady gaze during the treatment.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CXLO Corneal Strengthening Solution and UVA Illumination DeviceCXLO Corneal Strengthening Solution	Combination product	Group 1, Group 2, Group 3

Primary outcome

Change From Baseline in Corrected Distance Visual Acuity (CDVA)
Time frame: Baseline and 6 and 12 months
Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline

2 secondary outcomes

Change From Baseline in Uncorrected Distance Visual Acuity (UCVA)
Time frame: Baseline and 6 and 12 months
Change From Baseline in Maximum Keratometry (KMax)
Time frame: Baseline and 6 and 12 months

Results and safety

Results posted to the registry on 12 Jan 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1	745	612
Group 2	735	597
Group 3	748	623

Primary outcome: Change From Baseline in Corrected Distance Visual Acuity (CDVA)

Time frame: Baseline and 6 and 12 months. Mean (Standard Error). Unit: logMAR

Measure	Group 1 n = 542	Group 2 n = 534	Group 3 n = 529
6 months	-0.058 (0.0088)	-0.068 (0.0094)	-0.064 (0.0104)
12 months	-0.074 (0.0119)	-0.060 (0.0127)	-0.071 (0.0176)

Population analysed: Keratoconus subjects completing assessment

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 12 months. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1	0 of 750 (0%)	0 of 750 (0%)	0 of 750
Group 2	0 of 745 (0%)	0 of 745 (0%)	0 of 745
Group 3	1 of 752 (0.1%)	0 of 752 (0%)	0 of 752

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36173242Epstein RJ, Belin MW, Gravemann D, Littner R, Rubinfeld RS. EpiSmart Crosslinking for Keratoconus: A Phase 2 Study. Cornea. 2023 Jul 1;42(7):858-866. doi: 10.1097/ICO.0000000000003136. Epub 2022 Sep 28.
Individual participant dataSharing planned: No

Related trials for Keratoconus

RecruitingObservational study
UNITY DX Cornea Study
Tomography
Not yet recruiting
Performance Evaluation of the OCUTOP Hand-held Corneal Topographer
Corneal Topography, Dry Eye Syndromes
Recruiting
Proof-of-Concept for a Novel Optical Aperture Contact Lens in Presbyopia and Keratoconus
Keratoconus, Presbyopia
RecruitingObservational study
A Study to Test the Diagnostic Potential of Brillouin Microscopy for Corneal Ectasia
Keratoconus, Ectasia
Enrolling by invitationObservational study
Corneal Biomechanical Analysis Using Brillouin Microscopy
Keratoconus, Keratoconus, Unstable

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gregg J Berdy, MD, FACS principal investigator

Ophthalmology Associates, St. Louis, MO

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CXLO Corneal Strengthening Solution and UVA Illumination Device in people with Keratoconus and Corneal Diseases, run by Cxlusa at 9 sites in United States.

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 8 inclusion and 7 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: stopped early, as of the sponsor's last update on 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2022). 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?

Change From Baseline in Corrected Distance Visual Acuity (CDVA) (time frame: Baseline and 6 and 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 NCT03029104, which also lists 1 linked publication.

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 12 Jan 2022.