AUDREY: Dose Ranging Study to Assess the Efficacy and Safety of Voclosporin Ophthalmic Solution in Subjects With Dry Eye Syndrome
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 |
---|---|---|
|
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
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
- 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
- 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
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.- AUR-VOS-2019-01
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
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 |
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
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 |
clinicaltrials@auriniapharma.com |
- AUR-VOS-2019-01