Clinical trial NCT04498182: A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease
Official title: A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (COMET-1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dry Eye Disease
Lead sponsor: Aerie Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-08-04
Enrollment: 369
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2b, multicenter, vehicle-controlled, double-masked, randomized study. All subjects enrolled will have dry eye disease. The study consists of Screening and Baseline visits to determine eligibility, followed by efficacy assessments at Day 14 (Visit 3), 28 (Visit 4) and 84 (Visit 5/Study Exit). Safety will be assessed at all study visits.

Detailed description: At the end of the Screening Visit, all qualified subjects will be assigned to administer AR-15512 vehicle twice a day to both eyes for 14 days (vehicle run-in period). After the vehicle run-in period, subjects will be re-evaluated for signs and symptoms of Dry Eye Disease (DED). Subjects who requalify based on inclusion/exclusion criteria will be randomized in a 1:1:1 ratio to receive AR-15512 0.0014% (lower dose), AR-15512 0.003% (higher dose) or AR-15512 vehicle administered as 1 drop in each eye twice daily for 84 days.

This study will utilize a Controlled Adverse Environment (CAE) chamber, which serves to (1) minimize the factors that could impact the evaluation (temperature, humidity, and airflow) and (2) stress the ocular surface in a safe, standardized, controlled, and reproducible manner. Subjects will be exposed to the CAE for approximately 90 minutes during each CAE visit. Subjects will be exposed to the CAE at the Screening and Baseline visits as well as on Day 28 (Visit 4) and Day 84 (Visit 5). Efficacy endpoints will be evaluated pre- and post- exposure to the CAE.

Aerie Pharmaceuticals was acquired by Alcon on November 22, 2022.

Eligibility criteria: Key Inclusion Criteria:

* Previous history of dry eye disease (DED) within the previous 6 months;
* Have used and/or desired to use artificial tears for DED symptoms within 2 months prior to the Screening visit;
* Signs and symptoms of DED at the Screening and Baseline visits;
* Best Corrected Visual Acuity (BCVA) of 20/200 (+0.70 LogMAR) or better in both eyes at both the Screening and Baseline visits;
* Other protocol-specified inclusion criteria may apply.

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 diseases which, in the opinion of the investigator, may interfere with study findings or interpretation;
* Use of contact lenses in either eye within 7 days prior to the Screening visit or planned use during the study;
* Regular use of ocular medications or nutritional supplements as specified in the protocol within 30 days prior to the Screening visit;
* Positive pregnancy test at Screening or Baseline visits or currently breastfeeding.
* Other protocol-specified exclusion criteria may apply.

Primary outcomes:
measure: Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
Secondary outcomes:
measure: Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28
timeFrame: Day 28
measure: Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84
timeFrame: Day 84
measure: Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84
timeFrame: Day 84
measure: Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28
timeFrame: Day 28
measure: Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84
timeFrame: Day 84
measure: Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28
timeFrame: Day 28
measure: Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84
timeFrame: Day 84
measure: Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28
timeFrame: Day 28
measure: Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28
timeFrame: Day 28
measure: Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84
timeFrame: Day 84
measure: Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28
timeFrame: Day 28
measure: Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84
timeFrame: Day 84
measure: Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14
timeFrame: Baseline (Day 1) (pre-treatment), Day 14
measure: Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14
timeFrame: Day 14
measure: Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14
timeFrame: Baseline (Day 1) (pre-treatment), Day 14
measure: Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14
timeFrame: Day 14
measure: Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14
timeFrame: Baseline (Day 1) (pre-treatment), Day 14
measure: Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14
timeFrame: Day 14
measure: Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14
timeFrame: Baseline (Day 1) (pre-treatment), Day 14
measure: Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14
timeFrame: Day 14
measure: Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
measure: Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28
timeFrame: Baseline (Day 1) (pre-treatment), Day 28
measure: Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84
timeFrame: Baseline (Day 1) (pre-treatment), Day 84
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Cornea and Cataract Consultants of Arizona
state: Arizona
city: Newport Beach
country: United States
facility: Eye Research Foundation
state: California
city: Colorado Springs
country: United States
facility: Vision Institute
state: Colorado
city: Carmel
country: United States
facility: Midwest Cornea Associates, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Michael Washburn Center for Ophthalmic Research, LLC
state: Indiana
city: Louisville
country: United States
facility: The Eye Care Institute
state: Kentucky
city: Andover
country: United States
facility: Andover Eye Associates
state: Massachusetts
city: Raynham
country: United States
facility: Andover Eye Associates
state: Massachusetts
city: Hamel
country: United States
facility: Complete Eye Care of Medina
state: Minnesota
city: Kansas City
country: United States
facility: Moyes Eye Center
state: Missouri
city: Shelby
country: United States
facility: Vita Eye Clinic
state: North Carolina
city: Memphis
country: United States
facility: Total Eye Care, PA
state: Tennessee
city: Smyrna
country: United States
facility: Advancing Vision Research, LLC
state: Tennessee
city: Clinton
country: United States
facility: Alpine Research Organization, Inc,
state: Utah
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
Study officials:
affiliation: Alcon Research, LLC
name: Scientific Advisor, Clinical Research and Development
role: STUDY_DIRECTOR
References: