Keratoconjunctivitis Sicca
Conditions
Keywords
KCS, dry eye, cyclosporine
Brief summary
This is a randomized, double-masked, vehicle-controlled study of the safety and efficacy of OTX-101 (0.09% cyclosporine nanomicellar solution) in the treatment of keratoconjunctivitis sicca to be conducted at approximately 50 sites.
Interventions
DRUGcyclosporine
DRUGvehicle of OTX-101
Sponsors
Sun Pharmaceutical Industries Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* History of dry eye syndrome (KCS) for a period of at least 6 months * Clinical diagnosis of bilateral KCS * Lissamine green conjunctival staining sum score of ≥ 3 to ≤ 9 out of a total possible score of 12 (scoring excludes superior zones 2 and 4) in the same eye at both the Screening and Baseline Visits. * Global symptom score (SANDE) ≥ 40 mm at both the Screening and Baseline Visits * Corrected Snellen visual acuity (VA) of better than 20/200 in each eye.
Exclusion criteria
* Use of cyclosporine ophthalmic emulsion 0.05% (Restasis®) within 3 months prior to the Screening Visit. * Previous treatment failure (lack of efficacy) with cyclosporine ophthalmic emulsion 0.05% (Restasis). * Diagnosis of Sjögren's disease ˃ 5 years prior to the Screening Visit. * Clinical diagnosis or any history of seasonal and/or perennial allergic conjunctivitis. * Use of systemic or topical medications within 7 days prior to the Screening Visit or during the study period that are known to cause dry eye. * Use of any topical ophthalmic medications, prescription (including anti-glaucoma medications) or over the counter (including artificial tears), other than the assigned study medication during the study period. * Current active eye disease other than dry wyw syndrome (i.e., any disease for which topical or systemic ophthalmic medication is necessary). * History of herpes keratitis. * Corneal transplant * Corneal refractive surgery within 6 months prior to the Screening Visit or postoperative refractive surgery symptoms of dryness that have not resolved. * Cataract surgery within 3 months prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tear Production | Baseline and 12 weeks | Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Conjunctival Staining | Baseline and 12 weeks | change from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots) |
| Central Corneal Staining | Baseline and 12 weeks | change from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale. |
| Symptom Score | Baseline and 12 weeks | change from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: 1. frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and 2. severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement. |
Countries
United States
Participant flow
Pre-assignment details
One subject in OTX-101 0.09% group, was never treated with study medication and is not included in any of analysis sets Additionally, because the subjects in the ITT analysis set were analyzed as randomized, one subject who erroneously received OTX-101 0.09%, was included in the Vehicle group for purposes of efficacy analysis.
Participants by arm
| Arm | Count |
|---|---|
| OTX-101 0.09% 0.09% cyclosporine nanomicellar ophthalmic solution | 371 |
| Vehicle vehicle of OTX-101 | 373 |
| Total | 744 |
Baseline characteristics
| Characteristic | Vehicle | Total | OTX-101 0.09% |
|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 14.68 | 59.0 years STANDARD_DEVIATION 14.4 | 58.4 years STANDARD_DEVIATION 14.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 23 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 86 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 305 Participants | 615 Participants | 310 Participants |
| Sex: Female, Male Female | 311 Participants | 626 Participants | 315 Participants |
| Sex: Female, Male Male | 62 Participants | 118 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 372 | 0 / 372 |
| other Total, other adverse events | 130 / 372 | 66 / 372 |
| serious Total, serious adverse events | 6 / 372 | 2 / 372 |
Outcome results
Primary
Tear Production
Percentage of Eyes with Increase from Baseline of ≥ 10 mm in Schirmer's Test Score
Time frame: Baseline and 12 weeks
Population: Intent to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OTX-101 0.09% | Tear Production | 16.6 Percentage of eyes |
| Vehicle | Tear Production | 9.2 Percentage of eyes |
Secondary
Central Corneal Staining
change from baseline in central corneal staining score (fluorescein, modified NEI/FDA scale) at 12 weeks. The Expanded National Eye Institute (NEI)/Industry Workshop Scale for Corneal Staining Score was used to grade each of the 5 areas of the cornea on a 0 (No punctate stain in area) to 4 (Severe diffuse (coalescent) macropunctate stain of the area) scale.
Time frame: Baseline and 12 weeks
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OTX-101 0.09% | Central Corneal Staining | -0.28 score on a scale | Standard Deviation 0.533 |
| Vehicle | Central Corneal Staining | -0.26 score on a scale | Standard Deviation 0.588 |
Secondary
Conjunctival Staining
change from baseline in total conjunctival staining score (lissamine green, modified National Eye Institute scale) at 12 weeks. Conjunctival Lissamine Green Staining Grades ranged from 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots)
Time frame: Baseline and 12 weeks
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OTX-101 0.09% | Conjunctival Staining | -1.53 score on a scale | Standard Deviation 1.927 |
| Vehicle | Conjunctival Staining | -1.16 score on a scale | Standard Deviation 2.2064 |
Secondary
Symptom Score
change from baseline in modified Symptom Assessment in Dry Eye (SANDE) score at 12 weeks. A modified SANDE instrument was used to evaluate dry eye symptoms at each visit. Subjects were asked to indicate: 1. frequency of dry and irritated eyes on a scale of 0 (rarely) to 100 (all the time); and 2. severity of dry eyes on a scale of 0 (very mild) to 100 (severe) The global symptom score is the square root of the frequency score times the severity score and will be completed at each visit. (range 0 to 100) Negative change from baseline indicates improvement.
Time frame: Baseline and 12 weeks
Population: Intent to treat population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OTX-101 0.09% | Symptom Score | -18.8 score on a scale | Standard Deviation 24.08 |
| Vehicle | Symptom Score | -19.1 score on a scale | Standard Deviation 23.14 |