CXL: Corneal Collagen Cross-linking for Progressive Keratoconus

• Sponsor: Glaukos Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00647699
• Collaborator: (none)
• Enrollment: 147
• Locations: 10
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 14.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Prospective, randomized multicenter study to determine the safety and effectiveness of performing cornea collagen cross-linking (CXL) using riboflavin and UVA light in eyes with progressive keratoconus.

Condition or Disease	Intervention/Treatment	Phase
Progressive Keratoconus	Drug: riboflavin ophthalmic solution; Device: UVA Irradiation	Phase 3

Detailed Description

This was a sham controlled study for the first three months. Patients had one eye designated as the study eye and were randomized to receive one of two study treatments (CXL or sham) in their study eye. The patients were evaluated at 1, 3, 6, and 12 months. At month 3 or later patients had the option of receiving CXL treatment in both the sham and non-study eye.

Study Design

• Study Type: Interventional
• Actual Enrollment: 147 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking in Eyes With Progressive Keratoconus
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Corneal Collagen Cross-linking (CXL) Treatment Group riboflavin ophthalmic solution and UVA irradiation	Drug: riboflavin ophthalmic solution; riboflavin 0.1% ophthalmic solution (approximately 32 drops, or 1.6 mL); Device: UVA Irradiation; UVA light (365 nm at an irradiance of 3 mW/cm2) for 30 minutes; Other Names: UV-X Illumination System
Sham Comparator: Control Group riboflavin ophthalmic solution without UVA irradiation.	Drug: riboflavin ophthalmic solution; riboflavin 0.1% ophthalmic solution (approximately 32 drops, or 1.6 mL)

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Maximum Keratometry (Kmax) [baseline,12 months]

   The primary efficacy parameter was corneal curvature, as measured by maximum keratometry (Kmax) in the study eyes. Study success was defined as a difference of ≥1 D in the mean change in Kmax from baseline to 12 months between the CXL group and control group. Keratometry was measured manually and by pentacam.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of keratoconus

• Documented progression over previous 24 months

• Decreased BSCVA

• Must complete all study visits

Exclusion Criteria:

• Prior corneal surgery or Intacs

• History of delayed wound healing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Shiley Eye Center	La Jolla	California	United States	92093
2	Gordon -Weiss Vision Institute	San Diego	California	United States	91222
3	Center for Excellence in Eye Care	Miami	Florida	United States	33176
4	Price Vision Group	Indianapolis	Indiana	United States	46260
5	Durrie Vision	Kansas City	Kansas	United States	66211
6	Wilmer Eye Institute at Johns Hopkins University	Baltimore	Maryland	United States	21287
7	Minnesota Eye Consultants	Minneapolis	Minnesota	United States	55404
8	Cornea & Laser Eye Institute; Hersh Vision Group	Teaneck	New Jersey	United States	07666
9	Edward Harkness Eye Institute at Columbia University Medical Center	New York	New York	United States	10032
10	Ophthalmic Consultants of Long Island	Rockville Centre	New York	United States	11570

Sponsors and Collaborators

• Glaukos Corporation

Investigators

• Principal Investigator: Peter Hersh, MD, Cornea and Laser Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Glaukos Corporation
• ClinicalTrials.gov Identifier: NCT00647699
• Other Study ID Numbers: UVX-002
• First Posted: Apr 1, 2008
• Last Update Posted: Apr 26, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by Glaukos Corporation: keratoconus; cross-linking; riboflavin; UVA light; cornea
• Additional relevant MeSH terms: Keratoconus; Riboflavin; Ophthalmic Solutions

Study Results

Participant Flow

Arm/Group Title	Corneal Collagen Cross-linking (CXL) Treatment Group	Control Group
Arm/Group Description	riboflavin ophthalmic solution and UVA irradiation (365 nm at an irradiance of 3 mW/cm2) for 30 minutes	riboflavin ophthalmic solution without UVA irradiation
Period Title: Overall Study
STARTED	73	74
COMPLETED	65	62
NOT COMPLETED	8	12

Baseline Characteristics

Arm/Group Title	Corneal Collagen Cross-linking (CXL) Treatment Group	Control Group	Total
Arm/Group Description	riboflavin ophthalmic solution and UVA irradiation (365 nm at an irradiance of 3 mW/cm2) for 30 minutes	riboflavin ophthalmic solution without UVA irradiation	Total of all reporting groups
Overall Participants	73	74	147
Age (Count of Participants)
<=18 years	7 9.6%	3 4.1%	10 6.8%
Between 18 and 65 years	66 90.4%	71 95.9%	137 93.2%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	19 26%	24 32.4%	43 29.3%
Male	54 74%	50 67.6%	104 70.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 9.6%	3 4.1%	10 6.8%
Not Hispanic or Latino	31 42.5%	36 48.6%	67 45.6%
Unknown or Not Reported	35 47.9%	35 47.3%	70 47.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 1.4%	1 0.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 9.6%	7 9.5%	14 9.5%
White	54 74%	61 82.4%	115 78.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	12 16.4%	5 6.8%	17 11.6%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Maximum Keratometry (Kmax)
Description	The primary efficacy parameter was corneal curvature, as measured by maximum keratometry (Kmax) in the study eyes. Study success was defined as a difference of ≥1 D in the mean change in Kmax from baseline to 12 months between the CXL group and control group. Keratometry was measured manually and by pentacam.
Time Frame	baseline,12 months

Outcome Measure Data

Analysis Population Description

The ITT (intent to treat) population consisted of all treated subjects, analyzed according to the treatment actually received. For the sham study eyes that received CXL treatment after baseline, the last Kmax measurement recorded prior to receiving CXL treatment was used in the analysis for later time points.

Arm/Group Title	Corneal Collagen Cross-linking (CXL) Treatment Group	Control Group
Arm/Group Description	riboflavin ophthalmic solution and UVA irradiation (365 nm at an irradiance of 3 mW/cm2) for 30 minutes	riboflavin ophthalmic solution without UVA irradiation
Measure Participants	73	74
Mean (Standard Deviation) [diopters]	-1.7 (4.7)	0.6 (2.8)

Adverse Events

Time Frame	3 months
Arm/Group Title	Corneal Collagen Cross-linking (CXL) Treatment Group		Control Group
Arm/Group Description	riboflavin ophthalmic solution and UVA irradiation (365 nm at an irradiance of 3 mW/cm2) for 30 minutes		riboflavin ophthalmic solution without UVA irradiation
All Cause Mortality
	Corneal Collagen Cross-linking (CXL) Treatment Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Corneal Collagen Cross-linking (CXL) Treatment Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/73 (0%)		3/74 (4.1%)
Eye disorders
ulcerative keratitis	0/73 (0%)	0	1/74 (1.4%)	1
Infections and infestations
Appendicitis	0/73 (0%)	0	1/74 (1.4%)	1
Injury, poisoning and procedural complications
infectious cat bite	0/73 (0%)	0	1/74 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Corneal Collagen Cross-linking (CXL) Treatment Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	57/73 (78.1%)		25/74 (33.8%)
Eye disorders
Corneal opacity	35/73 (47.9%)	43	1/74 (1.4%)	1
Eye pain	13/73 (17.8%)	13	3/74 (4.1%)	3
Punctate keratitis	13/73 (17.8%)	16	8/74 (10.8%)	8
Corneal striae	11/73 (15.1%)	11	5/74 (6.8%)	5
Corneal epithelial defect	10/73 (13.7%)	11	1/74 (1.4%)	1
Vision blurred	9/73 (12.3%)	12	1/74 (1.4%)	1
Conjunctival hyperaemia	7/73 (9.6%)	7	1/74 (1.4%)	1
Photophobia	6/73 (8.2%)	6	0/74 (0%)	0
Eyelid oedema	5/73 (6.8%)	5	0/74 (0%)	0
Visual acuity reduced	5/73 (6.8%)	5	6/74 (8.1%)	8
Dry Eye	4/73 (5.5%)	5	2/74 (2.7%)	2
Eye irritation	4/73 (5.5%)	4	1/74 (1.4%)	1
Eye oedema	4/73 (5.5%)	4	0/74 (0%)	0
Anterior chamber flare	3/73 (4.1%)	3	0/74 (0%)	0
Corneal disorder	3/73 (4.1%)	3	0/74 (0%)	0
Lacrimation increased	3/73 (4.1%)	3	0/74 (0%)	0
Corneal oedema	2/73 (2.7%)	2	0/74 (0%)	0
Diplopia	2/73 (2.7%)	2	1/74 (1.4%)	1
Foreign body sensation in eye	2/73 (2.7%)	2	0/74 (0%)	0
Glare	2/73 (2.7%)	2	1/74 (1.4%)	1
Ocular hyperaemia	2/73 (2.7%)	2	1/74 (1.4%)	1
Visual impairment	2/73 (2.7%)	2	1/74 (1.4%)	1
Corneal scar	2/73 (2.7%)	2	2/74 (2.7%)	2
Nervous system disorders
Headache	2/73 (2.7%)	2	0/74 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Site has the right to publish or communicate study results upon the earlier of: (a) publication of a multi-center publication of the Study results coordinated by Sponsor; or (b) submission of the Study data by Sponsor to the FDA; provided that the Sponsor reviews the proposed communication of results within ninety (90) days in advance of its release. Sponsor can request delay of publication or data release to allow for filing of patent application prior to the publication or release.