Progressive Keratoconus
Conditions
Brief summary
To evaluate the safety and efficacy of epithelium-on corneal collagen cross-linking (CXL) in impeding the progression of, and/or reducing corneal curvature (Kmax) in eyes with progressive keratoconus. Epithelium-on CXL uses a formulation that allows the riboflavin to penetrate the cornea without the need to remove the epithelium, the outer most layer of the cornea.
Detailed description
Up to 275 study eyes with progressive keratoconus will be enrolled. Study eyes will be randomized in a 2:1 ratio to receive CXL treatment or sham/control treatment.The primary efficacy endpoint is a difference of ≥ 1 diopter between treatment groups in the mean change in Kmax from baseline to Month 6.
Interventions
DRUGTest Article A
Riboflavin Ophthalmic Solution A
DRUGTest Article B
Riboflavin Ophthalmic Solution B
DRUGPlacebo
Placebo Vehicle of Test Article
DEVICEKXL medical device system
Mock UVA light source
Sponsors
Glaukos Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomization was by eye (active or sham). However an individual participant could receive active/active, active/untreated, sham/sham, sham/untreated or active/sham
Eligibility
Sex/Gender
ALL
Age
12 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Be between 12 and 55 years of age, male or female, of any race; 2. Provide written informed consent and sign a HIPAA form. Subjects who are under the age of 18 (or have not yet reached the age of majority per local regulations) will need to sign an assent form as well as having a parent or legal guardian sign an informed consent 3. Ability to read English or Spanish to complete the NEI-VFQ 25 questionnaire; 4. Willingness and ability to follow all instructions and comply with schedule for follow-up visits; 5. For females capable of becoming pregnant, agree to have urine pregnancy testing performed prior to randomization of each study eye; must not be lactating, and must agree to use a medically acceptable form of birth control for at least one week prior to the randomization visit, and continue to use the method for one month following the treatment. Acceptable forms for birth control are spermicide with barrier, oral contraceptive, injectable or implantable method of contraception, transdermal contraceptive, intrauterine device, or surgical sterilization of partner. For non-sexually active females, abstinence will be considered an acceptable form of birth control. Women considered capable of becoming pregnant include all females who have experienced menarche and have not experienced menopause (as defined by amenorrhea for greater than 12 consecutive months) or have not undergone successful surgical sterilization (e.g. hysterectomy, bilateral tubal ligation, or bilateral oophorectomy); 6. Having topographic and clinical evidence of keratoconus
Exclusion criteria
1. Contraindications, sensitivity or known allergy to the use of the test article(s) or their components; 2. If female, be pregnant, nursing or planning a pregnancy or have a positive urine pregnancy test prior to the randomization or treatment of either eye or during the course of the study; 3. Previous ocular condition (other than refractive error) in the eye to be treated that may predispose the eye for future complications. 4. A history of delayed epithelial healing in the eye to be treated or a current condition that may interfere with or prolong epithelial healing; 5. A history of previous corneal cross-linking treatment in the eye to be treated; 6. Have used an investigational drug or device within 30 days of screening or be concurrently enrolled in another investigational drug or device trial within 30 days of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Treatment Groups in the Change From Baseline to Month 6 in Kmax | 6 months | Mean difference of at least 1 diopter in Kmax change from baseline to Month 6 between treatment groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Treatment Groups in the Change From Baseline to Month 12 in Kmax | 12 months | Difference between the CXL and Sham/Control treatment groups in the change from baseline to Month 12 in Kmax |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at eye clinics and were required to meet inclusion/exclusion criteria prior to enrollment
Pre-assignment details
280 eyes of 201 subjects were randomized in a 2:1 treatment allocation. Of the 280 randomized eyes, 279 were treated: 189 eyes of 156 subjects received CXL treatment & 90 eyes of 83 subjects received Sham/Control, for a total of 239 treatments. Of the 201 unique subjects, 118 received CXL only (in 1 or both eyes), 45 received Sham/Control only (in 1 or both eyes), and 38 subjects received CXL in 1 eye and Sham/Control in the other eye.
Participants by arm
| Arm | Count |
|---|---|
| Epithelium-on CXL Treatment Group Study eye receives riboflavin ophthalmic solution A, riboflavin ophthalmic solution B and irradiated using KXL High Power System
Riboflavin Ophthalmic Solution A Riboflavin Ophthalmic Solution B: KXL High Power System | 156 |
| Epithelium-on CXL Treatment Group Study eye receives riboflavin ophthalmic solution A, riboflavin ophthalmic solution B and irradiated using KXL High Power System
Riboflavin Ophthalmic Solution A Riboflavin Ophthalmic Solution B: KXL High Power System | 189 |
| Sham Treatment/Control Group Sham eye receives Placebo (the vehicle of Riboflavin Ophthalmic Solution) and Mock UVA light source
Placebo KXL High Power System providing mock UVA light source | 83 |
| Sham Treatment/Control Group Sham eye receives Placebo (the vehicle of Riboflavin Ophthalmic Solution) and Mock UVA light source
Placebo KXL High Power System providing mock UVA light source | 90 |
| Total | 518 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Epithelium-on CXL Treatment Group | Sham Treatment/Control Group | Total |
|---|---|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 9.75 | 29.5 years STANDARD_DEVIATION 9.67 | 30.0 years STANDARD_DEVIATION 9.9 |
| Mean Kmax (D) | 59.4 Diopters STANDARD_DEVIATION 9.1 | 59.3 Diopters STANDARD_DEVIATION 9.1 | 59.4 Diopters STANDARD_DEVIATION 9.1 |
| Race/Ethnicity, Customized Ethnicity: Hispanic or Latino | 28 participants | 68 participants | 36 participants |
| Race/Ethnicity, Customized Ethnicity: Not Hispanic or Latino | 128 participants | 15 participants | 165 participants |
| Race/Ethnicity, Customized Race: Asian | 3 participants | 4 participants | 5 participants |
| Race/Ethnicity, Customized Race: Black or African American | 27 participants | 18 participants | 36 participants |
| Race/Ethnicity, Customized Race: Native Hawaiian or Other Pacific Islander | 3 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Race: Other | 11 participants | 6 participants | 15 participants |
| Race/Ethnicity, Customized Race: White | 112 participants | 54 participants | 142 participants |
| Sex/Gender, Customized Female | 47 participants | 28 participants | 62 participants |
| Sex/Gender, Customized Male | 109 participants | 55 participants | 139 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 189 | 0 / 90 | 0 / 118 | 0 / 45 | 0 / 38 |
| other Total, other adverse events | 170 / 189 | 63 / 90 | 1 / 118 | 0 / 45 | 2 / 38 |
| serious Total, serious adverse events | 1 / 189 | 0 / 90 | 2 / 118 | 0 / 45 | 1 / 38 |
Outcome results
Primary
Difference Between Treatment Groups in the Change From Baseline to Month 6 in Kmax
Mean difference of at least 1 diopter in Kmax change from baseline to Month 6 between treatment groups
Time frame: 6 months
Population: Intent-to-treat analysis set which included all randomized study eyes that had at least one post-treatment follow-up efficacy assessment. Missing post-baseline Kmax data were imputed using multiple imputation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Epithelium-on CXL Treatment Group | Difference Between Treatment Groups in the Change From Baseline to Month 6 in Kmax | -0.3 Diopters |
| Sham Treatment/Control Group | Difference Between Treatment Groups in the Change From Baseline to Month 6 in Kmax | 0.6 Diopters |
Comparison: Repeated measures mixed analysis of covariance modelp-value: 0.000495% CI: [-1.5, -0.4]ANCOVA
Secondary
Difference Between Treatment Groups in the Change From Baseline to Month 12 in Kmax
Difference between the CXL and Sham/Control treatment groups in the change from baseline to Month 12 in Kmax
Time frame: 12 months
Population: Intent-to-treat analysis set which included all randomized study eyes that had at least one post-treatment follow-up efficacy assessment. Missing post-baseline Kmax data were imputed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Epithelium-on CXL Treatment Group | Difference Between Treatment Groups in the Change From Baseline to Month 12 in Kmax | -0.4 Diopters |
| Sham Treatment/Control Group | Difference Between Treatment Groups in the Change From Baseline to Month 12 in Kmax | 0.7 Diopters |
Comparison: repeated measures mixed analysis of covariance modelp-value: <0.000195% CI: [-1.6, -0.6]ANCOVA