A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (COMET-1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 369
- 试验地点
- 14
- 主要终点
- Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
AR-15512 Ophthalmic Solution Higher Dose
AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes will be treated.
干预措施: AR-15512 Ophthalmic Solution (Drug)
AR-15512 Ophthalmic Solution Lower Dose
AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes will be treated.
干预措施: AR-15512 Ophthalmic Solution (Drug)
Vehicle
AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes will be treated.
干预措施: AR-15512 Ophthalmic Solution Vehicle (Drug)
结局指标
主要结局
Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28
时间窗: Baseline (Day 1) (pre-treatment), Day 28
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more positive change value indicates a better outcome. One eye (study eye) contributed data to the analysis. This is a co-primary endpoint.
Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28
时间窗: Baseline (Day 1) (pre-treatment), Day 28
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 millimeters (mm) (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. This is a co-primary endpoint.
次要结局
- Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28(Day 28)
- Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84(Day 84)
- Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84(Day 84)
- Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28(Day 28)
- Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84(Day 84)
- Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28(Baseline (Day 1) (pre-treatment), Day 28)
- Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28(Day 28)
- Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84(Day 84)
- Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28(Baseline (Day 1) (pre-treatment), Day 28)
- Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28(Day 28)
- Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28(Baseline (Day 1) (pre-treatment), Day 28)
- Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28(Day 28)
- Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84(Day 84)
- Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28(Baseline (Day 1) (pre-treatment), Day 28)
- Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84(Day 84)
- Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28(Baseline (Day 1) (pre-treatment), Day 28)
- Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14(Day 14)
- Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14(Baseline (Day 1) (pre-treatment), Day 14)
- Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28(Day 28)
- Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14(Baseline (Day 1) (pre-treatment), Day 14)
- Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84(Baseline (Day 1) (pre-treatment), Day 84)
- Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14(Day 14)
- Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14(Baseline (Day 1) (pre-treatment), Day 14)
- Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14(Day 14)
- Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14(Baseline (Day 1) (pre-treatment), Day 14)
- Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14(Day 14)
- 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(Baseline (Day 1) (pre-treatment), Day 84)
- 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(Baseline (Day 1) (pre-treatment), Day 28)
- Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28(Baseline (Day 1) (pre-treatment), Day 28)
- Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84(Baseline (Day 1) (pre-treatment), Day 84)