Trial Outcomes & Findings for Ocular Tolerability of Voclosporin Ophthalmic Solution Versus Restasis® in Subjects With Dry Eye Disease (NCT NCT03597139)

NCT ID: NCT03597139

Last Updated: 2021-07-08

Results Overview

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".

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: 1-minute Post Dose 1 installation (Day 1)
• Results posted on: 2021-07-08

Participant Flow

Recruitment period from August 2018 - December 2018

Participant milestones

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

Reasons for withdrawal

Measure	Voclosporin Ophthalmic Solution (VOS) 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Overall Study Adverse Event	3	0
Overall Study Protocol Non-compliance	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator	Total n=100 Participants Total of all reporting groups
Age, Continuous	57.5 years STANDARD_DEVIATION 14.51 • n=5 Participants	60.2 years STANDARD_DEVIATION 15.08 • n=7 Participants	58.9 years STANDARD_DEVIATION 14.78 • n=5 Participants
Sex: Female, Male Female	42 Participants n=5 Participants	38 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	38 Participants n=5 Participants	39 Participants n=7 Participants	77 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	36 Participants n=7 Participants	71 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Duration of Dry Eye Disease	2.85 years n=5 Participants	2.67 years n=7 Participants	2.85 years n=5 Participants

PRIMARY outcome

Timeframe: 1-minute Post Dose 1 installation (Day 1)

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1	7.9 mm Standard Deviation 17.95	3.5 mm Standard Deviation 13.30

SECONDARY outcome

Timeframe: 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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Drop Discomfort Post Dose Instillation on Day 28	11.8 mm Standard Deviation 20.64	6.1 mm Standard Deviation 17.79

SECONDARY outcome

Timeframe: Day 28

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Burning/Stinging Post Dose Instillation on Day 28	-12.3 mm Standard Deviation 33.22	-20.1 mm Standard Deviation 25.11

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Foreign Body Sensation Post Dose Instillation on Day 28	-19.7 mm Standard Deviation 35.8	-20.7 mm Standard Deviation 32.95

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Photophobia Post Dose Instillation on Day 28	-23.1 mm Standard Deviation 26.35	-26.2 mm Standard Deviation 25.91

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Eye Pain Post Dose Instillation on Day 28	-13.9 mm Standard Deviation 31.39	-19.9 mm Standard Deviation 28.62

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Eye Dryness Post Dose Instillation on Day 28	-35.0 mm Standard Deviation 27.59	-34.6 mm Standard Deviation 27.73

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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".

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Itching Post Dose Instillation on Day 28	-26.9 mm Standard Deviation 27.41	-28.1 mm Standard Deviation 30.88

SECONDARY outcome

Timeframe: Day 28

Population: Intent to Treat

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).

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in the Total of All Individual Symptom Severity Assessment Scores	-130.9 mm Standard Deviation 144.95	-149.6 mm Standard Deviation 126.16

SECONDARY outcome

Timeframe: Day 28

Population: Intent to Treat

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.

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) Frequency	-28.0 mm Standard Deviation 29.37	-37.9 mm Standard Deviation 27.24
Change From Baseline in Symptom Assessment in Dry Eye Score (SANDE) Severity	-24.9 mm Standard Deviation 34.06	-36.1 mm Standard Deviation 24.84

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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.

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Unanesthetized Schirmer Test Score Right Eye	8.2 mm Standard Deviation 10.64	3.3 mm Standard Deviation 8.39
Change From Baseline in Unanesthetized Schirmer Test Score Left Eye	8.5 mm Standard Deviation 10.52	3.0 mm Standard Deviation 9.03

SECONDARY outcome

Timeframe: 28 days

Population: Intent to Treat

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.

Outcome measures

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 Participants 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 Participants 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Change From Baseline in Fluorescein Corneal Staining (FCS) Score Left Eye	-2.2 mm Standard Deviation 2.90	-0.2 mm Standard Deviation 3.05
Change From Baseline in Fluorescein Corneal Staining (FCS) Score Right Eye	-2.2 mm Standard Deviation 3.15	-0.7 mm Standard Deviation 2.79

Adverse Events

Voclosporin Ophthalmic Solution (VOS)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Comparator

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Voclosporin Ophthalmic Solution (VOS) n=51 participants at risk 0.2% VOS, Twice Daily (BID), both eyes for 28 days Voclosporin Ophthalmic Solution: Investigational Drug	Comparator n=49 participants at risk 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days Restasis®: Comparator
Eye disorders Ocular Discomfort	13.7% 7/51 • Number of events 9 • 28 days +/- 3 days (follow-up period)	10.2% 5/49 • Number of events 5 • 28 days +/- 3 days (follow-up period)
General disorders Instillation site pain	5.9% 3/51 • Number of events 3 • 28 days +/- 3 days (follow-up period)	2.0% 1/49 • Number of events 1 • 28 days +/- 3 days (follow-up period)
Eye disorders Lacrimation increased	0.00% 0/51 • 28 days +/- 3 days (follow-up period)	4.1% 2/49 • Number of events 3 • 28 days +/- 3 days (follow-up period)

Additional Information

Mary Palmen

Aurinia Pharmaceuticals

Phone: 1 (250) 744-2487

Email: clinicaltrials@auriniapharma.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place