Dry Eye
Conditions
Keywords
Dry Eye, Calcineurin Inhibitors
Brief summary
Evaluate the tolerability, efficacy and safety of VOS versus Restasis® in subjects with mild to moderate Dry Eye Disease (DED).
Detailed description
This is a Phase 2, multi-center, Investigator-masked, randomized, parallel-group study to evaluate the tolerability, efficacy and safety of VOS versus Restasis® over a 28-day treatment period in subjects with mild to moderate DED. Approximately 90 subjects will be randomized to either VOS or Restasis® at approximately 7 centers located in the US
Interventions
Investigational Drug
DRUGRestasis®
Comparator
Sponsors
Aurinia Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Intervention model description
This is a Phase 2, multi-center, Investigator-masked, randomized, parallel-group study to evaluate the tolerability, efficacy and safety of VOS versus Restasis® over a 28-day treatment period in subjects with mild to moderate DED. Approximately 90 subjects will be randomized to either VOS or Restasis® at approximately 7 centers located in the US.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have a best corrected visual acuity (BCVA) in both eyes of +0.7 logarithm of the Minimum Angle of Resolution (logMAR) or better as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. 2. Have a documented history of DED in both eyes supported by a previous clinical diagnosis. 3. Have ongoing DED, as defined by at least one eye (if one eye, the same eye) meeting all the following criteria: * A symptom severity score of ≥30 for Eye Dryness on a Visual Analog Scale (VAS) (0-100) * An unanesthetized Schirmer Tear Test (STT) score of ≥1 mm and ≤10 mm per 5 minutes (Note: STT Score obtained at Visit 1) * Evidence of ocular surface staining (total fluorescein staining score of at least 3 \[0-15 scale\]). 4. Have normal lid anatomy.
Exclusion criteria
1. Have any known hypersensitivity or contraindication to study treatments (including excipients), topical anesthetics or vital dyes. 2. Be unable to demonstrate correct instillation of over-the-counter (OTC) ocular lubricant. 3. Report discomfort in both eyes from instillation of OTC ocular lubricant during Visit 2 (based on score of ≥30 on the Drop Discomfort VAS). 4. Have used Restasis® (cyclosporine ophthalmic emulsion) within 30 days prior to Visit 1. 5. Have used Restasis® for more than 1 month (if prior use is reported). 6. Have used Xiidra® (lifitegrast ophthalmic solution) within 14 days prior to Visit 1. 7. Have had corneal graft surgery in either eye within 1 year. 8. Have recent or current evidence of ocular infection or inflammation in either eye. 9. Have current evidence of clinically significant blepharitis (defined as requiring lid hygiene therapy), conjunctivitis, or a history of herpes simplex or zoster keratitis in either eye.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1 | 1-minute Post Dose 1 installation (Day 1) | Drop Discomfort was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment 1 minute post-instillation on Day 1. The VAS scale is 0 - 100, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28 | Day 28 | Burning/Stinging was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no burning/stinging and 100 corresponds to worst burning/stinging. |
| Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28 | 28 days | Foreign Body Sensation was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no foreign body sensation and 100 corresponds to worst foreign body sensation. |
| Change From Baseline in Photophobia Post Dose Instillation on Day 28 | 28 days | Photophobia was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no photophobia and 100 corresponds to worst photophobia. |
| Change From Baseline in Eye Pain Post Dose Instillation on Day 28 | 28 days | Eye pain was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no eye pain and 100 corresponds to worst eye pain. |
| Change From Baseline in Eye Dryness Post Dose Instillation on Day 28 | 28 days | Eye dryness was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no eye dryness and 100 corresponds to worst eye dryness. |
| Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28 | Day 28 | Drop Discomfort was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment 1 minute post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort. |
| Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores | Day 28 | The Individual Symptom Severity Assessment Visual Analog Scale (VAS) includes Burning/Stinging (scale 0 - 100; 0 = no Burning/Stinging, 100 = worst Burning/Stinging), Foreign Body Sensation (scale 0 - 100; 0 = no Foreign Body Sensation, 100 = worst Foreign Body Sensation), Photophobia (scale 0 - 100; 0 = no Photophobia, 100 = worst Photophobia), Eye Pain (scale 0 - 100; 0 = no Eye Pain, 100 = worst Eye Pain), Eye Dryness (scale 0 - 100; 0 = no Eye Dryness, 100 = worst Eye Dryness), and Itching (scale 0 - 100; 0 = no Itching, 100 = worst Itching). The total sum of all 6 symptoms (Burning/Stinging, Foreign Body Sensation, Photophobia, Eye Pain, Eye Dryness, Itching) were evaluated (scale 0 - 600; 0 = no visual symptoms, 600 = worst visual symptoms). |
| Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) | Day 28 | The Symptom Assessment in Dry Eye (SANDE) is a subjective rating performed by the subjects for the frequency and severity of their dry eye symptoms. The total length of the line is 100mm. For Frequency of Symptoms 0mm = rarely and 100mm = all the time. For Severity of Symptoms 0mm = very mild and 100mm = very severe. Subjects were asked to subjectively rate the frequency and severity of their symptoms by placing an X on the relevant horizontal line. The length of the line between the rarely or very mild starting point and the first point where the subject's mark crosses each line was measured and recorded in millimeters. |
| Change From Baseline in Unanesthetized Schirmer Test Score | 28 days | The Schirmer Test Score recorded tear production on test strips. The Schirmer tear test was conducted 1 hour following administration of VOS/Comparator and 20 minutes following fluorescein corneal staining. Using a ruler and/or the millimeters recorded on the strips, a point halfway between the two lines was measured and this was recorded as the amount of wetting. Lower scores indicate less tear production and therefore a worse outcome. Normal tear production is ≥10mm of wetting on the test strip, and severe dry eye is \<5mm of wetting on the test strip. |
| Change From Baseline in Fluorescein Corneal Staining (FCS) Score | 28 days | The FCS score was summarized for each eye separately. Each of the 5 sections of cornea (superior, inferior, nasal, temporal, central) were graded using the National Eye Institute (NEI) scale; 0, 1 (mild), 2 (moderate), or 3 (severe). The total score was obtained by summing each of the 5 sections of the cornea from 0 - 15. Lower scores indicate less staining and therefore a better outcome. |
| Change From Baseline in Itching Post Dose Instillation on Day 28 | 28 days | Itching was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no itching and 100 corresponds to worst itching. |
Countries
United States
Participant flow
Recruitment details
Recruitment period from August 2018 - December 2018
Participants by arm
| Arm | Count |
|---|---|
| Voclosporin Ophthalmic Solution (VOS) 0.2% VOS, Twice Daily (BID), both eyes for 28 days
Voclosporin Ophthalmic Solution: Investigational Drug | 51 |
| Comparator 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days
Restasis®: Comparator | 49 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Protocol Non-compliance | 1 | 0 |
Baseline characteristics
| Characteristic | Voclosporin Ophthalmic Solution (VOS) | Comparator | Total |
|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 14.51 | 60.2 years STANDARD_DEVIATION 15.08 | 58.9 years STANDARD_DEVIATION 14.78 |
| Duration of Dry Eye Disease | 2.85 years | 2.67 years | 2.85 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants | 39 Participants | 77 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 8 Participants | 21 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 35 Participants | 36 Participants | 71 Participants |
| Sex: Female, Male Female | 42 Participants | 38 Participants | 80 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 49 |
| other Total, other adverse events | 10 / 51 | 6 / 49 |
| serious Total, serious adverse events | 0 / 51 | 0 / 49 |
Outcome results
Primary
Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1
Drop Discomfort was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment 1 minute post-instillation on Day 1. The VAS scale is 0 - 100, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort.
Time frame: 1-minute Post Dose 1 installation (Day 1)
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1 | 7.9 mm | Standard Deviation 17.95 |
| Comparator | Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1 | 3.5 mm | Standard Deviation 13.3 |
p-value: 0.149195% CI: [-1.7, 10.9]ANCOVA
Secondary
Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28
Burning/Stinging was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no burning/stinging and 100 corresponds to worst burning/stinging.
Time frame: Day 28
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28 | -12.3 mm | Standard Deviation 33.22 |
| Comparator | Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28 | -20.1 mm | Standard Deviation 25.11 |
p-value: 0.212895% CI: [-3.7, 16.5]ANCOVA
Secondary
Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28
Drop Discomfort was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment 1 minute post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no discomfort and 100 corresponds to maximal discomfort.
Time frame: Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28 | 11.8 mm | Standard Deviation 20.64 |
| Comparator | Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28 | 6.1 mm | Standard Deviation 17.79 |
p-value: 0.118795% CI: [-1.6, 13.9]ANCOVA
Secondary
Change From Baseline in Eye Dryness Post Dose Instillation on Day 28
Eye dryness was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no eye dryness and 100 corresponds to worst eye dryness.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Eye Dryness Post Dose Instillation on Day 28 | -35.0 mm | Standard Deviation 27.59 |
| Comparator | Change From Baseline in Eye Dryness Post Dose Instillation on Day 28 | -34.6 mm | Standard Deviation 27.73 |
p-value: 0.766695% CI: [-12.6, 9.3]ANCOVA
Secondary
Change From Baseline in Eye Pain Post Dose Instillation on Day 28
Eye pain was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no eye pain and 100 corresponds to worst eye pain.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Eye Pain Post Dose Instillation on Day 28 | -13.9 mm | Standard Deviation 31.39 |
| Comparator | Change From Baseline in Eye Pain Post Dose Instillation on Day 28 | -19.9 mm | Standard Deviation 28.62 |
p-value: 0.178795% CI: [-2.7, 14.1]ANCOVA
Secondary
Change From Baseline in Fluorescein Corneal Staining (FCS) Score
The FCS score was summarized for each eye separately. Each of the 5 sections of cornea (superior, inferior, nasal, temporal, central) were graded using the National Eye Institute (NEI) scale; 0, 1 (mild), 2 (moderate), or 3 (severe). The total score was obtained by summing each of the 5 sections of the cornea from 0 - 15. Lower scores indicate less staining and therefore a better outcome.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Fluorescein Corneal Staining (FCS) Score | Right Eye | -2.2 mm | Standard Deviation 3.15 |
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Fluorescein Corneal Staining (FCS) Score | Left Eye | -2.2 mm | Standard Deviation 2.9 |
| Comparator | Change From Baseline in Fluorescein Corneal Staining (FCS) Score | Left Eye | -0.2 mm | Standard Deviation 3.05 |
| Comparator | Change From Baseline in Fluorescein Corneal Staining (FCS) Score | Right Eye | -0.7 mm | Standard Deviation 2.79 |
Comparison: Left Eyep-value: 0.000395% CI: [-3.2, -1]ANCOVA
Comparison: Right Eyep-value: 0.003895% CI: [-2.6, -0.5]ANCOVA
Secondary
Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28
Foreign Body Sensation was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no foreign body sensation and 100 corresponds to worst foreign body sensation.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28 | -19.7 mm | Standard Deviation 35.8 |
| Comparator | Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28 | -20.7 mm | Standard Deviation 32.95 |
p-value: 0.840895% CI: [-11.8, 9.6]ANCOVA
Secondary
Change From Baseline in Itching Post Dose Instillation on Day 28
Itching was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no itching and 100 corresponds to worst itching.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Itching Post Dose Instillation on Day 28 | -26.9 mm | Standard Deviation 27.41 |
| Comparator | Change From Baseline in Itching Post Dose Instillation on Day 28 | -28.1 mm | Standard Deviation 30.88 |
p-value: 0.808295% CI: [-10.7, 8.4]ANCOVA
Secondary
Change From Baseline in Photophobia Post Dose Instillation on Day 28
Photophobia was assessed using the Individual Symptom Severity Assessment Visual Analog Scale (VAS) where the subject will complete the assessment post-instillation on Day 28. The VAS scale is 0 - 100, where 0 corresponds to no photophobia and 100 corresponds to worst photophobia.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Photophobia Post Dose Instillation on Day 28 | -23.1 mm | Standard Deviation 26.35 |
| Comparator | Change From Baseline in Photophobia Post Dose Instillation on Day 28 | -26.2 mm | Standard Deviation 25.91 |
p-value: 0.535695% CI: [-6.1, 11.6]ANCOVA
Secondary
Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE)
The Symptom Assessment in Dry Eye (SANDE) is a subjective rating performed by the subjects for the frequency and severity of their dry eye symptoms. The total length of the line is 100mm. For Frequency of Symptoms 0mm = rarely and 100mm = all the time. For Severity of Symptoms 0mm = very mild and 100mm = very severe. Subjects were asked to subjectively rate the frequency and severity of their symptoms by placing an X on the relevant horizontal line. The length of the line between the rarely or very mild starting point and the first point where the subject's mark crosses each line was measured and recorded in millimeters.
Time frame: Day 28
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) | Frequency | -28.0 mm | Standard Deviation 29.37 |
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) | Severity | -24.9 mm | Standard Deviation 34.06 |
| Comparator | Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) | Frequency | -37.9 mm | Standard Deviation 27.24 |
| Comparator | Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) | Severity | -36.1 mm | Standard Deviation 24.84 |
Comparison: Frequencyp-value: 0.096195% CI: [-1.7, 20.9]ANCOVA
Comparison: Severityp-value: 0.172295% CI: [-3.4, 18.7]ANCOVA
Secondary
Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores
The Individual Symptom Severity Assessment Visual Analog Scale (VAS) includes Burning/Stinging (scale 0 - 100; 0 = no Burning/Stinging, 100 = worst Burning/Stinging), Foreign Body Sensation (scale 0 - 100; 0 = no Foreign Body Sensation, 100 = worst Foreign Body Sensation), Photophobia (scale 0 - 100; 0 = no Photophobia, 100 = worst Photophobia), Eye Pain (scale 0 - 100; 0 = no Eye Pain, 100 = worst Eye Pain), Eye Dryness (scale 0 - 100; 0 = no Eye Dryness, 100 = worst Eye Dryness), and Itching (scale 0 - 100; 0 = no Itching, 100 = worst Itching). The total sum of all 6 symptoms (Burning/Stinging, Foreign Body Sensation, Photophobia, Eye Pain, Eye Dryness, Itching) were evaluated (scale 0 - 600; 0 = no visual symptoms, 600 = worst visual symptoms).
Time frame: Day 28
Population: Intent to Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores | -130.9 mm | Standard Deviation 144.95 |
| Comparator | Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores | -149.6 mm | Standard Deviation 126.16 |
p-value: 0.636295% CI: [-37, 60.3]ANCOVA
Secondary
Change From Baseline in Unanesthetized Schirmer Test Score
The Schirmer Test Score recorded tear production on test strips. The Schirmer tear test was conducted 1 hour following administration of VOS/Comparator and 20 minutes following fluorescein corneal staining. Using a ruler and/or the millimeters recorded on the strips, a point halfway between the two lines was measured and this was recorded as the amount of wetting. Lower scores indicate less tear production and therefore a worse outcome. Normal tear production is ≥10mm of wetting on the test strip, and severe dry eye is \<5mm of wetting on the test strip.
Time frame: 28 days
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Unanesthetized Schirmer Test Score | Left Eye | 8.5 mm | Standard Deviation 10.52 |
| Voclosporin Ophthalmic Solution (VOS) | Change From Baseline in Unanesthetized Schirmer Test Score | Right Eye | 8.2 mm | Standard Deviation 10.64 |
| Comparator | Change From Baseline in Unanesthetized Schirmer Test Score | Left Eye | 3.0 mm | Standard Deviation 9.03 |
| Comparator | Change From Baseline in Unanesthetized Schirmer Test Score | Right Eye | 3.3 mm | Standard Deviation 8.39 |
Comparison: Left Eyep-value: 0.005195% CI: [1.6, 8.9]ANCOVA
Comparison: Right Eyep-value: 0.010495% CI: [1.1, 8.4]ANCOVA