Ocular Tolerability of Voclosporin Ophthalmic Solution Versus Restasis® in Subjects With Dry Eye Disease

• Sponsor: Aurinia Pharmaceuticals Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03597139
• Collaborator: (none)
• Enrollment: 100
• Locations: 7
• Arms: 2
• Actual Duration (Months): 4
• Patients Per Site: 14.3
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

Evaluate the tolerability, efficacy and safety of VOS versus Restasis® in subjects with mild to moderate Dry Eye Disease (DED).

Condition or Disease	Intervention/Treatment	Phase
Dry Eye	Drug: Voclosporin Ophthalmic Solution; Drug: Restasis®	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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.
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: An Investigator-Masked, Randomized, Parallel-Group Study of the Ocular Tolerability of Voclosporin Ophthalmic Solution Versus Restasis® in Subjects With Dry Eye Disease
• Actual Study Start Date: Aug 13, 2018
• Actual Primary Completion Date: Nov 9, 2018
• Actual Study Completion Date: Dec 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Voclosporin ophthalmic solution (VOS) 0.2% VOS, Twice Daily (BID), both eyes for 28 days	Drug: Voclosporin Ophthalmic Solution; Investigational Drug; Other Names: 0.2% VOS
Active Comparator: Comparator 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days	Drug: Restasis®; Comparator; Other Names: RESTASIS® (cyclosporine ophthalmic emulsion) 0.05%

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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".

2. 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".

3. 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".

4. 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".

5. 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".

6. 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".

7. 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".

8. 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).

9. 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.

10. 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.

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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]).

1. 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

6. Have used Restasis® for more than 1 month (if prior use is reported).

7. Have used Xiidra® (lifitegrast ophthalmic solution) within 14 days prior to Visit 1.

8. Have had corneal graft surgery in either eye within 1 year.

9. Have recent or current evidence of ocular infection or inflammation in either eye.

10. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aurinia Investigative Center	Garden Grove	California	United States	92843
2	Aurinia Investigative Center	Mission Hills	California	United States	91345
3	Aurinia Investigative Center	Rancho Cordova	California	United States	95670
4	Aurinia Investigative Center	Kansas City	Missouri	United States	64111
5	Aurinia Investigative Center	Washington	Missouri	United States	63090
6	Aurinia Investigative Center	High Point	North Carolina	United States	27262
7	Aurinia Investigative Center	Memphis	Tennessee	United States	38119

Sponsors and Collaborators

• Aurinia Pharmaceuticals Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol: aur-vos-2017-01-protocol-v1_Redacted - Mar 12, 2018
• Study Protocol: aur-vos-2017-01-protocol-v2_Redacted - Jun 20, 2018
• Study Protocol: aur-vos-2017-01-protocol-v3_Redacted - Jul 2, 2018
• Statistical Analysis Plan - Sep 13, 2018

More Information

Publications

None provided.

• Responsible Party: Aurinia Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03597139
• Other Study ID Numbers: AUR-VOS-2017-01
• First Posted: Jul 24, 2018
• Last Update Posted: Jul 8, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Aurinia Pharmaceuticals Inc.: Dry Eye; Calcineurin Inhibitors
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Cyclosporine; Ophthalmic Solutions; Cyclosporins

Study Results

Participant Flow

Recruitment Details	Recruitment period from August 2018 - December 2018

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Period Title: Overall Study
STARTED	51	49
COMPLETED	47	49
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator	Total
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator	Total of all reporting groups
Overall Participants	51	49	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (14.51)	60.2 (15.08)	58.9 (14.78)
Sex: Female, Male (Count of Participants)
Female	42 82.4%	38 77.6%	80 80%
Male	9 17.6%	11 22.4%	20 20%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 25.5%	10 20.4%	23 23%
Not Hispanic or Latino	38 74.5%	39 79.6%	77 77%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 3.9%	3 6.1%	5 5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	13 25.5%	8 16.3%	21 21%
White	35 68.6%	36 73.5%	71 71%
More than one race	0 0%	1 2%	1 1%
Unknown or Not Reported	1 2%	1 2%	2 2%
Duration of Dry Eye Disease (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	2.85	2.67	2.85

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1
Description	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)

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	7.9 (17.95)	3.5 (13.30)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1491
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.6
	Confidence Interval	(2-Sided) 95%; -1.7 to 10.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	11.8 (20.64)	6.1 (17.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1187
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 95%; -1.6 to 13.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-12.3 (33.22)	-20.1 (25.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2128
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	6.4
	Confidence Interval	(2-Sided) 95%; -3.7 to 16.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-19.7 (35.8)	-20.7 (32.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8408
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -11.8 to 9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Photophobia Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-23.1 (26.35)	-26.2 (25.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5356
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.8
	Confidence Interval	(2-Sided) 95%; -6.1 to 11.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Eye Pain Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-13.9 (31.39)	-19.9 (28.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1787
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.7
	Confidence Interval	(2-Sided) 95%; -2.7 to 14.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Eye Dryness Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-35.0 (27.59)	-34.6 (27.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7666
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -12.6 to 9.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Itching Post Dose Instillation on Day 28
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-26.9 (27.41)	-28.1 (30.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8082
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -10.7 to 8.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Mean (Standard Deviation) [mm]	-130.9 (144.95)	-149.6 (126.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6362
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.6
	Confidence Interval	(2-Sided) 95%; -37 to 60.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE)
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Frequency	-28.0 (29.37)	-37.9 (27.24)
Severity	-24.9 (34.06)	-36.1 (24.84)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments	Frequency
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0961
	Comments	Frequency
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	9.6
	Confidence Interval	(2-Sided) 95%; -1.7 to 20.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments	Severity
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1722
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7.7
	Confidence Interval	(2-Sided) 95%; -3.4 to 18.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Unanesthetized Schirmer Test Score
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Left Eye	8.5 (10.52)	3.0 (9.03)
Right Eye	8.2 (10.64)	3.3 (8.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments	Left Eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0051
	Comments	Left Eye
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.2
	Confidence Interval	(2-Sided) 95%; 1.6 to 8.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments	Right Eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0104
	Comments	Right Eye
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 95%; 1.1 to 8.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Fluorescein Corneal Staining (FCS) Score
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)	Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Measure Participants	51	49
Left Eye	-2.2 (2.90)	-0.2 (3.05)
Right Eye	-2.2 (3.15)	-0.7 (2.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments	Left Eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments	Left Eye
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -3.2 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Add in RE LE info

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Voclosporin Ophthalmic Solution (VOS), Comparator
	Comments	Right Eye
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0038
	Comments	Right Eye
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.6 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	28 days +/- 3 days (follow-up period)
Arm/Group Title	Voclosporin Ophthalmic Solution (VOS)		Comparator
Arm/Group Description	0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug		0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
All Cause Mortality
	Voclosporin Ophthalmic Solution (VOS)		Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/49 (0%)
Serious Adverse Events
	Voclosporin Ophthalmic Solution (VOS)		Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	Voclosporin Ophthalmic Solution (VOS)		Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/51 (19.6%)		6/49 (12.2%)
Eye disorders
Ocular Discomfort	7/51 (13.7%)	9	5/49 (10.2%)	5
Lacrimation increased	0/51 (0%)	0	2/49 (4.1%)	3
General disorders
Instillation site pain	3/51 (5.9%)	3	1/49 (2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.