Back to resultsA Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512 (COMET-4)
Primary Purpose
Dry Eye Disease
Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
AR-15512 Ophthalmic Solution
Vehicle
Sponsored by
About this trial
This is an interventional treatment trial for Dry Eye Disease
Eligibility Criteria
Key Inclusion Criteria:
- Male or female, 18 years of age or older at baseline visit
- Have a previous history of DED, clinician diagnosed or patient reported, within the previous 12 months of the Baseline visit
- Have used or desired to use artificial tears for DED symptoms within 3 months prior to the Baseline visit
- Have a documented Schirmer test with or without topical anesthesia score ≥ 2 and < 10 mm/5 min in at least one eye within 1 year prior to the Baseline visit
- Total ocular surface staining score of ≥ 1 and ≤ 12 and no region = 5, based on the Oxford grading scheme at the Baseline visit
- Corrected visual acuity equal to or better than logMar +0.7 (Snellen equivalent equal to or better than 20/100), as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in both eyes at the Baseline visit
- Good general and ocular health, as determined by the investigator using medical history, ophthalmic examination and history, and vital signs (heart rate and blood pressure) at the Baseline visit
Key Exclusion Criteria:
- History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or subject safety
- Current evidence of other significant ophthalmic disease requiring topical medication (e.g. glaucoma, ocular hypertension), which may interfere with vision (e.g., cataract, macular degeneration) or other disease which the investigator believes may interfere with study findings or interpretation
- Use of contact lenses in either eye within 7 days prior to the Baseline visit or planned use during the study
- Use of any topical ocular anti-inflammatory medication within 30 days prior to the Baseline visit or anticipated use during the study (e.g., ocular cyclosporine [Restasis®, Cequa™], lifitegrast [Xiidra®], or any other prescription ophthalmic product for DED, topical ocular corticosteroid- or non-steroidal anti-inflammatory agents
- Use of topical ocular autologous serum within 30 days prior to the Baseline visit or anticipated use during the study
- Use of any topical ocular glaucoma medication within 30 days prior to the Baseline visit or anticipated use during the study
- Use of Tyrvara™ (varenicline solution, nasal spray 0.03mg) within 30 days prior to the Baseline visit or anticipated use during the study
- Use of medications for the treatment of severe DED and/or Meibomian gland disease such as oral pilocarpine, oral cevimeline, oral macrolides, oral tetracyclines, oral tetracycline derivatives, and oral retinoids within 30 days prior to the Baseline visit or anticipated use during the study
- Use of lid heating therapy (i.e., LipiFlow®, iLUX®) or Meibomian gland probing/therapeutic expression within 6 months prior to the Baseline visit or anticipated during the study
Sites / Locations
- Arizona Eye Center
- PRG - Arizona Eye Institute
- Global Research Management
- Macy Eye Center
- Eye Research Foundation
- Shultz Vision
- SightMD
- University Eye Specialists
- Piedmont Eye Center
- Periman Eye Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AR-15512 Ophthalmic Solution (0.003%)
Vehicle
Arm Description
0.003% AR-15512 to be administered BID for 365 days. Both eyes will be treated.
AR-15512 vehicle to be administered BID for 365 days. Both eyes will be treated.
Outcomes
Primary Outcome Measures
Adverse Events
Incidence of Adverse Events
Subjects will be verbally asked by clinic staff to report any changes to any aspect of their health (systemic or ocular) at each study visit. A low incidence indicates a better outcome.
Blood Pressure
Change from baseline
Each subjects systolic and diastolic blood pressure will be measured using an appropriate sphygmomanometer and will be recorded in mmHg. Minimal change from the start of the study indicates a better outcome.
Heart Rate
Change from Baseline
Each subjects heart rate will be measured using manual or automated methods and recorded in bpm. Minimal change from the start of the study indicates a better outcome.
Endothelial cell counts
Change from baseline
Specular microscopy will be used to measure cells in the central cornea to determine cell density which will be recorded. Minimal change from the start of the study indicates a better outcome.
Hematology, chemistry, and urinalysis
Change from baseline
A small volume of blood and urine will be collected from each subject and these samples will be sent to a laboratory to evaluate each subjects overall health. Values for each assessment will be recorded in their respective clinical units. Minimal change from the start of the study indicates a better outcome.
LogMAR Visual Acuity
Change from baseline
Each subject's vision will be assessed using an eye chart and the score will be recorded as the number of letters read. If a subject wears glasses, these will be worn during the test. Minimal change from the start of the study indicates a better outcome.
Early Treatment of Diabetic Retinopathy Study (ETDRS) Visual Acuity
Change from baseline
Change from baseline Each subject's vision will be assessed using a standardized eye chart and ETDRS testing procedure. The score will be recorded as the number of letters read. Minimal change from the start of the study indicates a better outcome.
Biomicroscopy
Change from baseline
With the aid of a microscope, the front part of the eyes and eyelids and the surface of the cornea will be examined and graded based on standard clinical scales and recorded as normal or abnormal. Minimal change from the start of the study indicates a better outcome.
Total ocular staining
Change from baseline
Dye is applied to the surface of the eye and the amount of dye that remains after several minutes will viewed through a microscope and graded using a standardized scale (0-5). Lower scores indicate a better outcome.
Intraocular pressure (IOP)
Change from baseline
A small tonometer device will be pressed against the surface of the eye to determine the pressure inside the eye. The pressure will be recorded in mmHg. Lower scores indicate a better outcome.
Dilated fundus exam
Change from baseline
The back of the eyes will be dilated, examined and graded based on standard clinical scales and recorded as normal or abnormal. Minimal change from the start of the study indicates a better outcome
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05493111
Brief Title
A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512
Acronym
COMET-4
Official Title
A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512, a Cold Thermoreceptor Modulator, for the Treatment of Dry Eye Disease (COMET-4)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aerie Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This will be a 12-month, multicenter, vehicle-controlled, double-masked, randomized Phase 3 study conducted at approximately 10 sites in the United States. All subjects enrolled will have dry eye disease (DED). The study will consist of a Baseline (Day 1) visit as well as visits at Day 14, Day 90, Day 180, Day 270, and Day 365 (Study Exit).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Qualified subjects will be enrolled in the study and randomized in a 2:1 ratio within each site to receive 0.003% AR-15512 or AR-15512 vehicle to be administered twice daily (BID) as 1 drop in each eye for 365 days.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
During the randomized treatment period, the investigator and site staff performing eligibility / efficacy and safety assessments and the subjects will be masked.
Allocation
Randomized
Enrollment
275 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AR-15512 Ophthalmic Solution (0.003%)
Arm Type
Experimental
Arm Description
0.003% AR-15512 to be administered BID for 365 days. Both eyes will be treated.
Arm Title
Vehicle
Arm Type
Placebo Comparator
Arm Description
AR-15512 vehicle to be administered BID for 365 days. Both eyes will be treated.
Intervention Type
Drug
Intervention Name(s)
AR-15512 Ophthalmic Solution
Intervention Description
Topical ocular administration of one drop in both eyes BID for 365 days.
Intervention Type
Drug
Intervention Name(s)
Vehicle
Intervention Description
Topical ocular administration of one drop in both eyes BID for 365 days.
Primary Outcome Measure Information:
Title
Adverse Events
Description
Incidence of Adverse Events
Subjects will be verbally asked by clinic staff to report any changes to any aspect of their health (systemic or ocular) at each study visit. A low incidence indicates a better outcome.
Time Frame
Day 1, 14, 90, 180, 270 & 365
Title
Blood Pressure
Description
Change from baseline
Each subjects systolic and diastolic blood pressure will be measured using an appropriate sphygmomanometer and will be recorded in mmHg. Minimal change from the start of the study indicates a better outcome.
Time Frame
Day 1, 14, 90, 180, 270 & 365
Title
Heart Rate
Description
Change from Baseline
Each subjects heart rate will be measured using manual or automated methods and recorded in bpm. Minimal change from the start of the study indicates a better outcome.
Time Frame
Time Frame: Day 1, 14, 90, 180, 270 & 365
Title
Endothelial cell counts
Description
Change from baseline
Specular microscopy will be used to measure cells in the central cornea to determine cell density which will be recorded. Minimal change from the start of the study indicates a better outcome.
Time Frame
Day 1 and 365
Title
Hematology, chemistry, and urinalysis
Description
Change from baseline
A small volume of blood and urine will be collected from each subject and these samples will be sent to a laboratory to evaluate each subjects overall health. Values for each assessment will be recorded in their respective clinical units. Minimal change from the start of the study indicates a better outcome.
Time Frame
Day 1, 180 & 365
Title
LogMAR Visual Acuity
Description
Change from baseline
Each subject's vision will be assessed using an eye chart and the score will be recorded as the number of letters read. If a subject wears glasses, these will be worn during the test. Minimal change from the start of the study indicates a better outcome.
Time Frame
Day 1, 14, 90, 180, 270 & 365
Title
Early Treatment of Diabetic Retinopathy Study (ETDRS) Visual Acuity
Description
Change from baseline
Change from baseline Each subject's vision will be assessed using a standardized eye chart and ETDRS testing procedure. The score will be recorded as the number of letters read. Minimal change from the start of the study indicates a better outcome.
Time Frame
Day 1 & 365
Title
Biomicroscopy
Description
Change from baseline
With the aid of a microscope, the front part of the eyes and eyelids and the surface of the cornea will be examined and graded based on standard clinical scales and recorded as normal or abnormal. Minimal change from the start of the study indicates a better outcome.
Time Frame
Day 1, 14, 90, 180, 270 & 365
Title
Total ocular staining
Description
Change from baseline
Dye is applied to the surface of the eye and the amount of dye that remains after several minutes will viewed through a microscope and graded using a standardized scale (0-5). Lower scores indicate a better outcome.
Time Frame
Day 1, 14, 90, 180, 270 & 365
Title
Intraocular pressure (IOP)
Description
Change from baseline
A small tonometer device will be pressed against the surface of the eye to determine the pressure inside the eye. The pressure will be recorded in mmHg. Lower scores indicate a better outcome.
Time Frame
Day 1, 14, 90, 180, 270 & 365
Title
Dilated fundus exam
Description
Change from baseline
The back of the eyes will be dilated, examined and graded based on standard clinical scales and recorded as normal or abnormal. Minimal change from the start of the study indicates a better outcome
Time Frame
Day 1, 14, 90, 180, 270 & 365
Other Pre-specified Outcome Measures:
Title
Minimum Plasma Concentration (Cmin)
Description
From the blood samples collected from each subject, the minimum amount of AR-15512, the test drug, that may be present in the blood will be measured at a laboratory. Each measure will be recorded in pg/ml. Lower numbers represent better outcome.
Time Frame
Day 1, 14 and 90
Title
Accumulation Ratio (Rcmax)
Description
From the blood samples collected from each subject, the amount of AR-15512, the test drug, that may have accumulated in the blood will be measured in a laboratory. Each measure will be recorded as a number based on a ratio (e.g. Cmax Day 90 / Cmax Day 1). Lower numbers represent better outcome.
Time Frame
Day 1, 14 and 90
Title
Time to Maximum Concentration (Tmax)
Description
From the blood samples collected from each subject, the time at which the highest amount of AR-15512, the test drug, is measured in the blood will be measured in a laboratory. Each measure will be recorded in hours/min/sec.
Time Frame
Day 1, 14 and 90
Title
Time to Last Detectable Concentration (Tlast)
Description
From the blood samples collected from each subject, the time at which the last detectable amount of AR-15512, the test drug, is measured in the blood will be measured in a laboratory. Each measure will be recorded in hours/min/sec. Lower number represents better outcome.
Time Frame
Day 1, 14 and 90
Title
Total Exposure (AUC0-last)
Description
From the blood samples collected from each subject, the overall amount of AR-15512, the test drug, in the blood from the start of dose administration to the time after dosing at which the last quantifiable concentration was observed will be measured in a laboratory. Each measure will be recorded in µg*h/L. Lower numbers represent better outcome.
Time Frame
Day 1, 14 and 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female, 18 years of age or older at baseline visit
Have a previous history of DED, clinician diagnosed or patient reported, within the previous 12 months of the Baseline visit
Have used or desired to use artificial tears for DED symptoms within 3 months prior to the Baseline visit
Have a documented Schirmer test with or without topical anesthesia score ≥ 2 and < 10 mm/5 min in at least one eye within 1 year prior to the Baseline visit
Total ocular surface staining score of ≥ 1 and ≤ 12 and no region = 5, based on the Oxford grading scheme at the Baseline visit
Corrected visual acuity equal to or better than logMar +0.7 (Snellen equivalent equal to or better than 20/100), as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) scale in both eyes at the Baseline visit
Good general and ocular health, as determined by the investigator using medical history, ophthalmic examination and history, and vital signs (heart rate and blood pressure) at the Baseline visit
Key Exclusion Criteria:
History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or subject safety
Current evidence of other significant ophthalmic disease requiring topical medication (e.g. glaucoma, ocular hypertension), which may interfere with vision (e.g., cataract, macular degeneration) or other disease which the investigator believes may interfere with study findings or interpretation
Use of contact lenses in either eye within 7 days prior to the Baseline visit or planned use during the study
Use of any topical ocular anti-inflammatory medication within 30 days prior to the Baseline visit or anticipated use during the study (e.g., ocular cyclosporine [Restasis®, Cequa™], lifitegrast [Xiidra®], or any other prescription ophthalmic product for DED, topical ocular corticosteroid- or non-steroidal anti-inflammatory agents
Use of topical ocular autologous serum within 30 days prior to the Baseline visit or anticipated use during the study
Use of any topical ocular glaucoma medication within 30 days prior to the Baseline visit or anticipated use during the study
Use of Tyrvara™ (varenicline solution, nasal spray 0.03mg) within 30 days prior to the Baseline visit or anticipated use during the study
Use of medications for the treatment of severe DED and/or Meibomian gland disease such as oral pilocarpine, oral cevimeline, oral macrolides, oral tetracyclines, oral tetracycline derivatives, and oral retinoids within 30 days prior to the Baseline visit or anticipated use during the study
Use of lid heating therapy (i.e., LipiFlow®, iLUX®) or Meibomian gland probing/therapeutic expression within 6 months prior to the Baseline visit or anticipated during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michelle Senchyna, PhD
Organizational Affiliation
Aerie Pharma
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Eye Center
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85225
Country
United States
Facility Name
PRG - Arizona Eye Institute
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Facility Name
Global Research Management
City
Glendale
State/Province
California
ZIP/Postal Code
91204
Country
United States
Facility Name
Macy Eye Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Eye Research Foundation
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Shultz Vision
City
Northridge
State/Province
California
ZIP/Postal Code
91325
Country
United States
Facility Name
SightMD
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
University Eye Specialists
City
Maryville
State/Province
Tennessee
ZIP/Postal Code
37803
Country
United States
Facility Name
Piedmont Eye Center
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24502
Country
United States
Facility Name
Periman Eye Institute
City
Seattle
State/Province
Washington
ZIP/Postal Code
98119
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Long-Term Safety Study Evaluating the Safety and Systemic Exposure of AR-15512
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