Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas
Sponsor
Cxlusa (Industry)
Overall Status
Terminated
CT.gov ID
NCT03029104
Collaborator
(none)
2,228
9
3
48.2
247.6
5.1
Study Details
Study Description
Brief Summary
This study will assess changes in visual acuity and corneal symmetry after corneal collagen cross-linking (CXL) of asymmetric corneas.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
2228 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Masking Description:
Visual acuity will be evaluated by an observer who is masked as to the treatment protocol to which study subjects have been assigned.
Primary Purpose:
Treatment
Official Title:
Collagen Cross-Linking With Ultraviolet-A in Asymmetric Corneas
Actual Study Start Date
:
Dec 21, 2016
Actual Primary Completion Date
:
Dec 27, 2020
Actual Study Completion Date
:
Dec 27, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Group 1 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. |
Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination Device
CXLO Corneal Strengthening Solution
|
| Active Comparator: Group 2 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. |
Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination Device
CXLO Corneal Strengthening Solution
|
| Active Comparator: Group 3 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. |
Combination Product: CXLO Corneal Strengthening Solution and UVA Illumination Device
CXLO Corneal Strengthening Solution
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Corrected Distance Visual Acuity (CDVA) [Baseline and 6 and 12 months]
Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline
Secondary Outcome Measures
- Change From Baseline in Uncorrected Distance Visual Acuity (UCVA) [Baseline and 6 and 12 months]
Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline
- Change From Baseline in Maximum Keratometry (KMax) [Baseline and 6 and 12 months]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
8 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- 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
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Schwartz Laser Eye Center | Scottsdale | Arizona | United States | 85260 |
| 2 | Goodman Eye Center | San Francisco | California | United States | 94115 |
| 3 | Cornea Consultants of Colorado | Littleton | Colorado | United States | 80120-4508 |
| 4 | Woolfson Eye Institute | Atlanta | Georgia | United States | 30328 |
| 5 | Chicago Cornea Consultants | Chicago | Illinois | United States | 60035 |
| 6 | Chicago Cornea Consultants, Ltd. | Hoffman Estates | Illinois | United States | 60169 |
| 7 | Ophthalmology Associates | Saint Louis | Missouri | United States | 63110 |
| 8 | Cleveland Eye Clinic | Brecksville | Ohio | United States | 44141 |
| 9 | Cornea Associates of Texas | Dallas | Texas | United States | 75231 |
Sponsors and Collaborators
- Cxlusa
Investigators
- Principal Investigator: Gregg J Berdy, MD, FACS, Ophthalmology Associates, St. Louis, MO
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Cxlusa
ClinicalTrials.gov Identifier:
NCT03029104
Other Study ID Numbers:
- CXL-005
First Posted:
Jan 24, 2017
Last Update Posted:
Jan 12, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
Yes
Keywords provided by Cxlusa
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| Arm/Group Description | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution |
| Period Title: Overall Study | |||
| STARTED | 745 | 735 | 748 |
| COMPLETED | 612 | 597 | 623 |
| NOT COMPLETED | 133 | 138 | 125 |
Baseline Characteristics
| Arm/Group Title | Group 1 | Group 2 | Group 3 | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | Total of all reporting groups |
| Overall Participants | 745 | 735 | 748 | 2228 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
32.6
(13.04)
|
32.4
(13.11)
|
32.6
(12.94)
|
32.5
(13.03)
|
| Age, Customized (participants) [Number] | ||||
| ≤21 years |
175
23.5%
|
163
22.2%
|
175
23.4%
|
513
23%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
221
29.7%
|
217
29.5%
|
220
29.4%
|
658
29.5%
|
| Male |
524
70.3%
|
518
70.5%
|
528
70.6%
|
1570
70.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
142
19.1%
|
118
16.1%
|
138
18.4%
|
398
17.9%
|
| Not Hispanic or Latino |
603
80.9%
|
617
83.9%
|
609
81.4%
|
1829
82.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
0.1%
|
1
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
2
0.3%
|
2
0.3%
|
3
0.4%
|
7
0.3%
|
| Asian |
32
4.3%
|
38
5.2%
|
31
4.1%
|
101
4.5%
|
| Native Hawaiian or Other Pacific Islander |
3
0.4%
|
7
1%
|
2
0.3%
|
12
0.5%
|
| Black or African American |
92
12.3%
|
89
12.1%
|
99
13.2%
|
280
12.6%
|
| White |
582
78.1%
|
573
78%
|
584
78.1%
|
1739
78.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
34
4.6%
|
26
3.5%
|
29
3.9%
|
89
4%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
745
100%
|
735
100%
|
748
100%
|
2228
100%
|
| Diagnosis of Keratoconus (Count of Participants) | ||||
| Count of Participants [Participants] |
644
86.4%
|
635
86.4%
|
643
86%
|
1922
86.3%
|
Outcome Measures
| Title | Change From Baseline in Corrected Distance Visual Acuity (CDVA) |
|---|---|
| Description | Changes in CDVA are reported as the value at 6 and 12 months minus the value at baseline |
| Time Frame | Baseline and 6 and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Keratoconus subjects completing assessment |
| Arm/Group Title | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| Arm/Group Description | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution |
| Measure Participants | 542 | 534 | 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)
|
| Title | Change From Baseline in Uncorrected Distance Visual Acuity (UCVA) |
|---|---|
| Description | Changes in UCVA are reported as the value at 6 and 12 months minus the value at baseline |
| Time Frame | Baseline and 6 and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Keratoconus subjects completing assessment |
| Arm/Group Title | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| Arm/Group Description | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution |
| Measure Participants | 541 | 533 | 528 |
| 6 months |
-0.0853
(0.0150)
|
-0.1099
(0.0150)
|
-0.0990
(0.0155)
|
| 12 months |
-0.0875
(0.0191)
|
-0.0696
(0.0197)
|
-0.1243
(0.0212)
|
| Title | Change From Baseline in Maximum Keratometry (KMax) |
|---|---|
| Description | 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. |
| Time Frame | Baseline and 6 and 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Keratoconus subjects completing assessment |
| Arm/Group Title | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| Arm/Group Description | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution |
| Measure Participants | 542 | 533 | 527 |
| 6 months |
-0.1979
(0.1069)
|
-0.4033
(0.1228)
|
-0.3673
(0.1125)
|
| 12 months |
-0.2859
(0.1204)
|
-0.5268
(0.1716)
|
-0.5256
(0.1707)
|
Adverse Events
| Time Frame | 12 months | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | A total of 2,228 subjects were randomized and treated in this study (Treated Analysis Set). 1,583 (71%) of these subjects received bilateral, simultaneous treatments. The Safety Analysis Set (SAS) is larger than the Treated Analysis Set because subjects who had an initial unilateral treatment and then had a subsequent procedure, appear in the SAS under two different treatment groups, if the subsequent treatment differs from the initial treatment. This occurred in 19 subjects. | |||||
| Arm/Group Title | Group 1 | Group 2 | Group 3 | |||
| Arm/Group Description | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | 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. CXLO Corneal Strengthening Solution and UVA Illumination Device: CXLO Corneal Strengthening Solution | |||
All Cause Mortality |
||||||
| Group 1 | Group 2 | Group 3 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/750 (0%) | 0/745 (0%) | 0/752 (0%) | |||
Serious Adverse Events |
||||||
| Group 1 | Group 2 | Group 3 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/750 (0%) | 0/745 (0%) | 1/752 (0.1%) | |||
| Infections and infestations | ||||||
| Diverticulitis | 0/750 (0%) | 0/745 (0%) | 1/752 (0.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Group 1 | Group 2 | Group 3 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/750 (0%) | 0/745 (0%) | 0/752 (0%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Chief Clinical Development Officer |
|---|---|
| Organization | CXL Ophthalmics, LLC |
| Phone | 339-234-6020 |
| info@cxlophthalmics.com |
Responsible Party:
Cxlusa
ClinicalTrials.gov Identifier:
NCT03029104
Other Study ID Numbers:
- CXL-005
First Posted:
Jan 24, 2017
Last Update Posted:
Jan 12, 2022
Last Verified:
Dec 1, 2021