AUDREY: Dose Ranging Study to Assess the Efficacy and Safety of Voclosporin Ophthalmic Solution in Subjects With Dry Eye Syndrome

Sponsor
Aurinia Pharmaceuticals Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04147650
Collaborator
(none)
508
9
4
11.8
56.4
4.8

Study Details

Study Description

Brief Summary

A Multi-Center, Phase 2/3, Randomized, Double-Masked, Parallel-Group, Vehicle-Controlled, Clinical Trial to Assess the Safety and Efficacy of Voclosporin Ophthalmic Solution (0.05%, 0.10%, 0.20%) Compared to Vehicle in Subjects with Dry Eye Syndrome.

Condition or Disease Intervention/Treatment Phase
  • Drug: 0.05% Voclosporin Ophthalmic Solution (VOS)
  • Drug: 0.10% VOS
  • Drug: 0.20% VOS
  • Drug: Vehicle Ophthalmic Solution
Phase 2/Phase 3

Detailed Description

This is a Phase 2/3, multi-center, randomized, double-masked, vehicle-controlled study to assess the efficacy and safety of three different concentrations of VOS when administered in both eyes (OU) twice a day (BID) over 12 weeks in subjects with mild to moderate DES. Subjects will undergo a 14- to 17-day run-in period in which VOS vehicle will be self-administered OU, BID. Subjects will be re-assessed to confirm they meet all of the inclusion criteria and none of the exclusion criteria. It is estimated that the study will enroll approximately 480 subjects across approximately 9 study centers. Eligible subjects will be randomized in a 1:1:1:1 ratio to one of the following study treatment groups after the 14- to 17-day run-in period.

Study Design

Study Type:
Interventional
Actual Enrollment :
508 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Subjects will be randomized to one of the following treatment groups: Investigational product (IP): one drop 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks, one drop 0.10% VOS OU BID over 12 weeks, or one drop 0.20% VOS OU BID over 12 weeks. Comparator: one drop VOS vehicle OU BID over 12 weeks.Subjects will be randomized to one of the following treatment groups:Investigational product (IP): one drop 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks, one drop 0.10% VOS OU BID over 12 weeks, or one drop 0.20% VOS OU BID over 12 weeks. Comparator: one drop VOS vehicle OU BID over 12 weeks.
Masking:
Double (Participant, Investigator)
Masking Description:
Double masked
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Masked, Vehicle-Controlled, Dose Ranging Study to Assess the Efficacy and Safety of Voclosporin Ophthalmic Solution (VOS) in Subjects With Dry Eye Syndrome (DES)
Actual Study Start Date :
Oct 14, 2019
Actual Primary Completion Date :
Sep 17, 2020
Actual Study Completion Date :
Oct 8, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: 0.05% Voclosporin Ophthalmic Solution (VOS)

0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks

Drug: 0.05% Voclosporin Ophthalmic Solution (VOS)
0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks

Experimental: 0.10% VOS

0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks

Drug: 0.10% VOS
0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks

Experimental: 0.20% VOS

0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks

Drug: 0.20% VOS
0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks

Placebo Comparator: Vehicle Ophthalmic Solution

Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks

Drug: Vehicle Ophthalmic Solution
Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks

Outcome Measures

Primary Outcome Measures

  1. Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT) [4 Weeks]

    Number of subjects with a ≥10 mm increase from baseline in STT at Week 4 in the study eye. The STT scale is a measure of tear production with a minimum of 0 mm and no there is no specified maximum for this scale.

Secondary Outcome Measures

  1. Change From Baseline in Eye Dryness [Value at 4 Weeks minus value at baseline]

    Mean change from baseline in Eye Dryness Visual Analogue Scale (VAS) in subjects with a baseline Eye Dryness VAS score ≥ 60 mm. Eye Dryness Visual Analogue Scale 0-100 mm, where 0 corresponds to "no discomfort" and 100 corresponds to "maximal discomfort."

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Be at least 18 years of age.

  • Have a documented history of Dry Eye prior to Visit 1.

  • Willing and able to follow protocol procedures and instructions.

Exclusion criteria:
  • Have undergone cataract or LASIK surgery within 1 year prior to Visit 1.

  • Recent or current evidence of infection or inflammation in either eye.

  • Current evidence of blepharitis, other meibomian gland dysfunction, conjunctivitis or history of herpes simplex or zoster keratitis in either eye.

  • Have used any investigational drug or device within 30 days prior to Visit 1.

  • Have used ophthalmic drugs (any topical eye medications) including prescription medication and over the counter (OTC) agents on the date of Visit 1.

  • Have worn contact lenses 24 hours prior to Visit 1.

  • Have used Xiidra® (lifitegrast) within 14 days prior to Visit 1.

  • Have used Calcineurin Inhibitors (CNIs) such as Restasis® (cyclosporin ophthalmic emulsion) or CequaTM within 30 days prior to Visit 1.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Aurinia Investigative Center Newport Beach California United States 92663
2 Aurinia Investigative Center Colorado Springs Colorado United States 80907
3 Aurinia Investigative Center Louisville Kentucky United States 40206
4 Aurinia Investigative Center Lewiston Maine United States 04240
5 Aurinia Investigative Center Andover Massachusetts United States 01810
6 Aurinia Investigative Center Raynham Massachusetts United States 02767
7 Aurinia Investigative Center Cranberry Township Pennsylvania United States 16066
8 Aurinia Investigative Center Memphis Tennessee United States 38119
9 Aurinia Investigative Center Nashville Tennessee United States 37205

Sponsors and Collaborators

  • Aurinia Pharmaceuticals Inc.

Investigators

  • Study Director: Mary Palmen, Aurinia Pharmaceuticals

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Aurinia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT04147650
Other Study ID Numbers:
  • AUR-VOS-2019-01
First Posted:
Nov 1, 2019
Last Update Posted:
Dec 10, 2021
Last Verified:
Dec 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.
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title 0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Arm/Group Description 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.05% Voclosporin Ophthalmic Solution (VOS): 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS: 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS: 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution: Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks
Period Title: Overall Study
STARTED 127 126 128 127
Modified Intent to Treat (mITT) 120 119 122 121
COMPLETED 116 107 121 120
NOT COMPLETED 11 19 7 7

Baseline Characteristics

Arm/Group Title 0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution Total
Arm/Group Description 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.05% Voclosporin Ophthalmic Solution (VOS): 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS: 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS: 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution: Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks Total of all reporting groups
Overall Participants 127 126 128 127 508
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
63.3
(11.82)
64.2
(11.27)
64.8
(10.47)
64.1
(12.43)
64.1
(11.49)
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
64
65
65
65
65
Sex: Female, Male (Count of Participants)
Female
96
75.6%
91
72.2%
88
68.8%
97
76.4%
372
73.2%
Male
31
24.4%
35
27.8%
40
31.3%
30
23.6%
136
26.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
7
5.5%
5
4%
7
5.5%
6
4.7%
25
4.9%
Not Hispanic or Latino
120
94.5%
120
95.2%
121
94.5%
121
95.3%
482
94.9%
Unknown or Not Reported
0
0%
1
0.8%
0
0%
0
0%
1
0.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
2
1.6%
1
0.8%
0
0%
1
0.8%
4
0.8%
Asian
7
5.5%
5
4%
9
7%
10
7.9%
31
6.1%
Native Hawaiian or Other Pacific Islander
1
0.8%
0
0%
0
0%
1
0.8%
2
0.4%
Black or African American
17
13.4%
16
12.7%
17
13.3%
22
17.3%
72
14.2%
White
96
75.6%
103
81.7%
99
77.3%
91
71.7%
389
76.6%
More than one race
4
3.1%
1
0.8%
3
2.3%
2
1.6%
10
2%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%

Outcome Measures

1. Primary Outcome
Title Number of Subjects With a ≥10 mm Increase From Baseline in Schirmer Tear Test (STT)
Description Number of subjects with a ≥10 mm increase from baseline in STT at Week 4 in the study eye. The STT scale is a measure of tear production with a minimum of 0 mm and no there is no specified maximum for this scale.
Time Frame 4 Weeks

Outcome Measure Data

Analysis Population Description
Modified intent to treat (mITT) number of subjects achieving ≥10 mm increase improvement at week 4
Arm/Group Title 0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Arm/Group Description 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.05% Voclosporin Ophthalmic Solution (VOS): 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS: 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS: 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution: Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks
Measure Participants 120 119 122 121
Number [participants]
12
9.4%
10
7.9%
13
10.2%
6
4.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.05% Voclosporin Ophthalmic Solution (VOS)
Comments 0.05 % VOS versus vehicle
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.1352
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.18
Confidence Interval (2-Sided) 95%
0.62 to 7.62
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.10% VOS
Comments 0.10% VOS versus vehicle
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.2823
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.78
Confidence Interval (2-Sided) 95%
0.49 to 6.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 0.20% VOS
Comments 0.20% VOS versus vehicle
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0889
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.41
Confidence Interval (2-Sided) 95%
0.70 to 8.30
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Change From Baseline in Eye Dryness
Description Mean change from baseline in Eye Dryness Visual Analogue Scale (VAS) in subjects with a baseline Eye Dryness VAS score ≥ 60 mm. Eye Dryness Visual Analogue Scale 0-100 mm, where 0 corresponds to "no discomfort" and 100 corresponds to "maximal discomfort."
Time Frame Value at 4 Weeks minus value at baseline

Outcome Measure Data

Analysis Population Description
The analysis was performed using all mITT subjects with a baseline eye dryness VAS ≥60 mm. Subjects without a Week 4 eye dryness VAS score were not included in this analysis.
Arm/Group Title 0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Arm/Group Description 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.05% Voclosporin Ophthalmic Solution (VOS): 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS: 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS: 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution: Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks
Measure Participants 85 84 86 89
Mean (Standard Deviation) [units on a scale]
-10.6
(21.80)
-9.3
(20.00)
-5.0
(17.68)
-7.0
(17.59)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 0.05% Voclosporin Ophthalmic Solution (VOS)
Comments 0.05% VOS versus vehicle
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.3604
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-9.6 to 4.3
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 0.10% VOS
Comments 0.10% VOS versus vehicle
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.3737
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value -2.6
Confidence Interval (2-Sided) 95%
-9.6 to 4.4
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 0.20% VOS
Comments 0.20% VOS versus vehicle
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.5307
Comments
Method ANCOVA
Comments
Method of Estimation Estimation Parameter Least square mean difference
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
-5.1 to 8.6
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Day 1 to Week 13
Adverse Event Reporting Description
Arm/Group Title 0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Arm/Group Description 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.05% Voclosporin Ophthalmic Solution (VOS): 0.05% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.10% VOS: 0.10% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks 0.20% VOS: 0.20% VOS, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks Vehicle Ophthalmic Solution: Vehicle Ophthalmic Solution, in both eyes (OU) twice a day (BID) over 12 weeks
All Cause Mortality
0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/127 (0%) 1/126 (0.8%) 0/128 (0%) 0/127 (0%)
Serious Adverse Events
0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/127 (0.8%) 3/126 (2.4%) 2/128 (1.6%) 3/127 (2.4%)
Cardiac disorders
Myocardial infarction 0/127 (0%) 0 1/126 (0.8%) 1 0/128 (0%) 0 0/127 (0%) 0
Gastrointestinal disorders
Small intestinal obstruction 0/127 (0%) 0 1/126 (0.8%) 1 0/128 (0%) 0 0/127 (0%) 0
General disorders
Systemic inflammatory response syndrome 1/127 (0.8%) 1 0/126 (0%) 0 0/128 (0%) 0 0/127 (0%) 0
Infections and infestations
Appendicitis 0/127 (0%) 0 0/126 (0%) 0 0/128 (0%) 0 1/127 (0.8%) 1
Injury, poisoning and procedural complications
Femur fracture 0/127 (0%) 0 1/126 (0.8%) 1 0/128 (0%) 0 0/127 (0%) 0
Head injury 0/127 (0%) 0 0/126 (0%) 0 0/128 (0%) 0 1/127 (0.8%) 1
Metabolism and nutrition disorders
Fluid overload 0/127 (0%) 0 0/126 (0%) 0 1/128 (0.8%) 1 0/127 (0%) 0
Nervous system disorders
Carotid artery stenosis 0/127 (0%) 0 0/126 (0%) 0 1/128 (0.8%) 1 0/127 (0%) 0
Cerebrovascular accident 0/127 (0%) 0 0/126 (0%) 0 1/128 (0.8%) 1 0/127 (0%) 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 0/127 (0%) 0 0/126 (0%) 0 0/128 (0%) 0 1/127 (0.8%) 1
Other (Not Including Serious) Adverse Events
0.05% Voclosporin Ophthalmic Solution (VOS) 0.10% VOS 0.20% VOS Vehicle Ophthalmic Solution
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 29/127 (22.8%) 42/126 (33.3%) 44/128 (34.4%) 8/127 (6.3%)
General disorders
Instillation site pain 29/127 (22.8%) 30 42/126 (33.3%) 43 44/128 (34.4%) 47 8/127 (6.3%) 10

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

Name/Title Clinical Trial Support
Organization Aurinia Pharmaceuticals
Phone (250) 744-2487
Email clinicaltrials@auriniapharma.com
Responsible Party:
Aurinia Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:
NCT04147650
Other Study ID Numbers:
  • AUR-VOS-2019-01
First Posted:
Nov 1, 2019
Last Update Posted:
Dec 10, 2021
Last Verified:
Dec 1, 2021