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

An Investigator-Masked, Randomized, Parallel-Group Study of the Ocular Tolerability of Voclosporin Ophthalmic Solution Versus Restasis® in Subjects With Dry Eye Disease

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

Study Overview

• Status: Completed
• Conditions: Dry Eye
• Intervention / Treatment: Drug: Voclosporin Ophthalmic Solution; Drug: Restasis®

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 Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Garden Grove, California, United States, 92843
      • Aurinia Investigative Center
    • Mission Hills, California, United States, 91345
      • Aurinia Investigative Center
    • Rancho Cordova, California, United States, 95670
      • Aurinia Investigative Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Aurinia Investigative Center
    • Washington, Missouri, United States, 63090
      • Aurinia Investigative Center
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Aurinia Investigative Center
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Aurinia Investigative Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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".	1-minute Post Dose 1 installation (Day 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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".	Day 28
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".	Day 28
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".	28 days
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".	28 days
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".	28 days
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".	28 days
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".	28 days
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).	Day 28
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.	Day 28
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.	28 days
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.	28 days

Collaborators and Investigators

• Sponsor: Aurinia Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2018
• Primary Completion (Actual): November 9, 2018
• Study Completion (Actual): December 13, 2018

Study Registration Dates

• First Submitted: July 13, 2018
• First Submitted That Met QC Criteria: July 13, 2018
• First Posted (Actual): July 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Dry Eye; Calcineurin Inhibitors
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Pharmaceutical Solutions; Calcineurin Inhibitors; Ophthalmic Solutions; Cyclosporine; Cyclosporins
• Other Study ID Numbers: AUR-VOS-2017-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No