Dry Eye Syndrome, Keratoconjunctivitis Sicca
Conditions
Keywords
Dry Eye Calcineurin Inhibitors, Dry Eye Disease
Brief summary
A Multi-Center, Phase 2/3, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Clinical Trial to Assess the Safety and Efficacy of Voclosporin Ophthalmic Solution (0.05%, 0.10%, 0.20%) Compared to Vehicle in Subjects with Dry Eye Syndrome.
Detailed description
This is a Phase 2/3, multi-center, randomized, double-masked, vehicle-controlled study to assess the efficacy and safety of three different concentrations of VOS when administered in both eyes (OU) twice a day (BID) over 12 weeks in subjects with mild to moderate DES. Subjects will undergo a 14- to 17-day run-in period in which VOS vehicle will be self-administered OU, BID. Subjects will be re-assessed to confirm they meet all of the inclusion criteria and none of the exclusion criteria. It is estimated that the study will enroll approximately 480 subjects across approximately 9 study centers. Eligible subjects will be randomized in a 1:1:1:1 ratio to one of the following study treatment groups after the 14- to 17-day run-in period.
Interventions
DRUG0.05% Voclosporin Ophthalmic Solution (VOS)
0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks
DRUG0.10% VOS
0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks
DRUG0.20% VOS
0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks
DRUGVehicle Ophthalmic Solution
Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks
Sponsors
Aurinia Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double masked
Intervention model description
Subjects will be randomized to one of the following treatment groups: Investigational product (IP): one drop 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks, one drop 0.10% VOS OU BID over 12 weeks, or one drop 0.20% VOS OU BID over 12 weeks. Comparator: one drop VOS vehicle OU BID over 12 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Be at least 18 years of age. * Have a documented history of Dry Eye prior to Visit 1. * Willing and able to follow protocol procedures and instructions.
Exclusion criteria
* Have undergone cataract or LASIK surgery within 1 year prior to Visit 1. * Recent or current evidence of infection or inflammation in either eye. * Current evidence of blepharitis, other meibomian gland dysfunction, conjunctivitis or history of herpes simplex or zoster keratitis in either eye. * Have used any investigational drug or device within 30 days prior to Visit 1. * Have used ophthalmic drugs (any topical eye medications) including prescription medication and over the counter (OTC) agents on the date of Visit 1. * Have worn contact lenses 24 hours prior to Visit 1. * Have used Xiidra® (lifitegrast) within 14 days prior to Visit 1. * Have used Calcineurin Inhibitors (CNIs) such as Restasis® (cyclosporin ophthalmic emulsion) or CequaTM within 30 days prior to Visit 1.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT) | 4 Weeks | Number of subjects with a ≥10 mm increase from baseline in STT at Week 4 in the study eye. The STT scale is a measure of tear production with a minimum of 0 mm and no there is no specified maximum for this scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Eye Dryness | Value at 4 Weeks minus value at baseline | Mean change from baseline in Eye Dryness Visual Analogue Scale (VAS) in subjects with a baseline Eye Dryness VAS score ≥ 60 mm. Eye Dryness Visual Analogue Scale 0-100 mm, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 0.05% Voclosporin Ophthalmic Solution (VOS) 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks
0.05% Voclosporin Ophthalmic Solution (VOS): 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks | 127 |
| 0.10% VOS 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks
0.10% VOS: 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks | 126 |
| 0.20% VOS 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks
0.20% VOS: 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks | 128 |
| Vehicle Ophthalmic Solution Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks
Vehicle Ophthalmic Solution: Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks | 127 |
| Total | 508 |
Baseline characteristics
| Characteristic | Total | 0.05% Voclosporin Ophthalmic Solution (VOS) | 0.10% VOS | 0.20% VOS | Vehicle Ophthalmic Solution |
|---|---|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 11.49 | 64 years | 65 years | 65 years | 65 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 7 Participants | 5 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 482 Participants | 120 Participants | 120 Participants | 121 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 7 Participants | 5 Participants | 9 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 72 Participants | 17 Participants | 16 Participants | 17 Participants | 22 Participants |
| Race (NIH/OMB) More than one race | 10 Participants | 4 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 389 Participants | 96 Participants | 103 Participants | 99 Participants | 91 Participants |
| Sex: Female, Male Female | 372 Participants | 96 Participants | 91 Participants | 88 Participants | 97 Participants |
| Sex: Female, Male Male | 136 Participants | 31 Participants | 35 Participants | 40 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 127 | 1 / 126 | 0 / 128 | 0 / 127 |
| other Total, other adverse events | 29 / 127 | 42 / 126 | 44 / 128 | 8 / 127 |
| serious Total, serious adverse events | 1 / 127 | 3 / 126 | 2 / 128 | 3 / 127 |
Outcome results
Primary
Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT)
Number of subjects with a ≥10 mm increase from baseline in STT at Week 4 in the study eye. The STT scale is a measure of tear production with a minimum of 0 mm and no there is no specified maximum for this scale.
Time frame: 4 Weeks
Population: Modified intent to treat (mITT) number of subjects achieving ≥10 mm increase improvement at week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.05% Voclosporin Ophthalmic Solution (VOS) | Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT) | 12 participants |
| 0.10% VOS | Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT) | 10 participants |
| 0.20% VOS | Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT) | 13 participants |
| Vehicle Ophthalmic Solution | Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT) | 6 participants |
Comparison: 0.05 % VOS versus vehiclep-value: 0.135295% CI: [0.62, 7.62]Regression, Logistic
Comparison: 0.10% VOS versus vehiclep-value: 0.282395% CI: [0.49, 6.45]Regression, Logistic
Comparison: 0.20% VOS versus vehiclep-value: 0.088995% CI: [0.7, 8.3]Regression, Logistic
Secondary
Change From Baseline in Eye Dryness
Mean change from baseline in Eye Dryness Visual Analogue Scale (VAS) in subjects with a baseline Eye Dryness VAS score ≥ 60 mm. Eye Dryness Visual Analogue Scale 0-100 mm, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort.
Time frame: Value at 4 Weeks minus value at baseline
Population: The analysis was performed using all mITT subjects with a baseline eye dryness VAS ≥60 mm. Subjects without a Week 4 eye dryness VAS score were not included in this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 0.05% Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Eye Dryness | -10.6 units on a scale | Standard Deviation 21.8 |
| 0.10% VOS | Change From Baseline in Eye Dryness | -9.3 units on a scale | Standard Deviation 20 |
| 0.20% VOS | Change From Baseline in Eye Dryness | -5.0 units on a scale | Standard Deviation 17.68 |
| Vehicle Ophthalmic Solution | Change From Baseline in Eye Dryness | -7.0 units on a scale | Standard Deviation 17.59 |
Comparison: 0.05% VOS versus vehiclep-value: 0.360495% CI: [-9.6, 4.3]ANCOVA
Comparison: 0.10% VOS versus vehiclep-value: 0.373795% CI: [-9.6, 4.4]ANCOVA
Comparison: 0.20% VOS versus vehiclep-value: 0.530795% CI: [-5.1, 8.6]ANCOVA