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

• ClinicalTrials.gov Identifier: NCT03597139
• Recruitment Status: Completed
• First Posted: July 24, 2018
• Results First Posted: July 8, 2021
• Last Update Posted: July 8, 2021
• Sponsor: Aurinia Pharmaceuticals Inc.
• Information provided by (Responsible Party): Aurinia Pharmaceuticals Inc.

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 (Clinical Trial)
• 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.
• 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: August 13, 2018
• Actual Primary Completion Date: November 9, 2018
• Actual Study Completion Date: December 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 Name: 0.2% VOS
Active Comparator: Comparator; 0.05% cyclosporine ophthalmic emulsion (Restasis®) BID, both eyes for 28 days	Drug: Restasis®; Comparator; Other Name: RESTASIS® (cyclosporine ophthalmic emulsion) 0.05%

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Drop Discomfort Post Dose Instillation on Day 1 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Aurinia Investigative Center

Garden Grove, California, United States, 92843

Aurinia Investigative Center

Mission Hills, California, United States, 91345

Aurinia Investigative Center

Rancho Cordova, California, United States, 95670

United States, Missouri

Aurinia Investigative Center

Kansas City, Missouri, United States, 64111

Aurinia Investigative Center

Washington, Missouri, United States, 63090

United States, North Carolina

Aurinia Investigative Center

High Point, North Carolina, United States, 27262

United States, Tennessee

Aurinia Investigative Center

Memphis, Tennessee, United States, 38119

Sponsors and Collaborators

Aurinia Pharmaceuticals Inc.

  Study Documents (Full-Text)

Documents provided by Aurinia Pharmaceuticals Inc.:

Study Protocol: aur-vos-2017-01-protocol-v1_Redacted  [PDF] March 12, 2018

Study Protocol: aur-vos-2017-01-protocol-v2_Redacted  [PDF] June 20, 2018

Study Protocol: aur-vos-2017-01-protocol-v3_Redacted  [PDF] July 2, 2018

Statistical Analysis Plan  [PDF] September 13, 2018

More Information

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

Individual Participant Data (IPD) Sharing Statement:

• 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; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Cyclosporine; Ophthalmic Solutions; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors; Pharmaceutical Solutions