A Randomized, Multicenter, Double-Masked, Vehicle-Controlled, Dose-Ranging Study of the Safety and Efficacy of OTX-101 in the Treatment of Keratoconjunctivitis Sicca
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 455
- 主要终点
- Conjunctival Staining
研究概览
简要总结
This is a Phase 2/3 study to evaluate the safety and efficacy of 2 different dose concentrations of OTX-101 dosed twice a day in both eyes for 84 days compared to placebo (vehicle) in patients with keratoconjunctivitis sicca (dry eye disease).
详细描述
Keratoconjunctivitis sicca (KCS) is a common multifactorial ophthalmologic disorder of the tears and ocular surface characterized by symptoms of burning, stinging, itching, grittiness, scratchiness, foreign body sensation, dryness, stickiness and tired eye sensation.
This study is the first clinical safety and efficacy study with OTX-101 and is designed to compare two dose concentrations of OTX-101 against vehicle (placebo) in reducing the signs and symptoms of KCS and evaluate safety when dosed twice a day in both eyes over an 84 day period.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects age 18 years or older on the date of informed consent.
- •All subjects must provide signed written consent prior to participation in any study-related procedures.
- •Patient-reported history of KCS for a period of at least 6 months.
- •Clinical diagnosis of bilateral KCS supported by OTX-101-2014-001 study assessments.
- •Lissamine green conjunctival staining sum score of ≥ 3 to ≤ 9 out of a total possible score of 12 (scoring excludes superior zones 2 and 4) in the same eye at Screening and Baseline.
- •Global symptom score ≥ 40 at both Screening and Baseline.
- •Corrected Snellen VA of better than 20/200 in each eye.
- •Willing to discontinue use of current dry eye therapy (including artificial tears or ocular lubricants) during the study as of the run-in period.
- •Female subjects of childbearing potential must have a negative urine pregnancy test at Screening. Women of childbearing potential (ie, women who are not either postmenopausal for one year or surgically sterile) must use an acceptable form of contraception throughout the study.
排除标准
- •Use of cyclosporine ophthalmic emulsion 0.05% (Restasis®) within 3 months prior to Screening.
- •Previous treatment failure (lack of efficacy) on cyclosporine ophthalmic emulsion 0.05% (Restasis).
- •Diagnosed with Sjögren's disease ˃5 years prior to Screening.
- •Clinical diagnosis of seasonal and perennial allergic conjunctivitis.
- •Use of systemic and topical medications that are known to cause dry eye within 7 days prior to Screening and throughout the study period. These include the following medications:
- •Immunomodulators (permitted if dose is stable for 3 months prior to screening and does not change during the study period)
- •Antihistamines (including over-the counter (OTC))
- •Cholinergics
- •Antimuscarinics
- •Tricyclic antidepressants
- •Phenothiazines
- •Retinoids
- •Oral omega-3 fatty acids (permitted if dose is stable for 3 months prior to Screening and does not change during the study period)
- •Use of any topical ophthalmic medications, prescription (including antiglaucoma medications) or OTC (including artificial tears), other than the assigned study medication during the study period.
- •Current active eye disease other than KCS (i.e., any disease for which topical or systemic ophthalmic medication is necessary).
- •History of herpes keratitis.
- •Unstable macular disease (e.g., age-related macular degeneration, diabetic maculopathy). Stable macular disease is defined as no reduction in central VA within 6 months prior to Screening.
- •Diagnosis of chronic uveitis.
- •Corneal transplant (e.g., penetrating keratoplasty, lamellar keratoplasty, Descemet's stripping endothelial keratoplasty (DSEK) ).
- •Corneal refractive surgery (e.g., laser-assisted in situ keratomileusis (LASIK]) photo refractive keratectomy (PRK), limbal relaxing incision (LRI) ) within 6 months prior to screening or postoperative refractive surgery symptoms of dryness that have not resolved.
- •Cataract surgery within 3 months prior to Screening.
- •Non-laser glaucoma surgery at any time; glaucoma laser procedures within 3 months prior to Screening.
- •Presence of punctal plugs or past history of permanent punctal occlusion (e.g., cautery).
- •Lagophthalmos or clinically significant eyelid margin irregularity of the study eye whether congenital or acquired.
- •Presence of conjunctivochalasis (i.e., mechanical blockage of the lower lid punctum by redundant conjunctiva).
- •Presence of pterygium in the study eye.
- •Unwilling to discontinue use of contact lenses during the duration of the study.
- •Preplanned elective surgery or hospitalization during the study period.
- •HIV-positive.
- •Unable to reliably report symptoms and history.
- •Has known hypersensitivity or contraindication to the study medication(s) or their components.
- •Has a history or presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the subject or confound the result(s) of the study.
- •Has a severe/serious ocular condition, or any other unstable medical condition that, in the Investigator's opinion, may preclude study treatment or follow-up.
- •Women who are pregnant or breastfeeding.
- •Participation in any drug or device clinical investigation within 30 days prior to entry into this study and/or during the period of study participation.
- •Previous randomization into this study.
研究组 & 干预措施
OTX-101 0.05%
OTX-101 0.05% ophthalmic solution 1 drop in both eyes BID for 84 days
干预措施: OTX-101 0.05% (Drug)
OTX-101 0.09%
OTX-101 0.09% ophthalmic solution 1 drop in both eyes BID for 84 days
干预措施: OTX-101 0.09% (Drug)
Vehicle
Vehicle of OTX-101 ophthalmic solution 1 drop in both eyes BID for 84 days
干预措施: Vehicle (Drug)
结局指标
主要结局
Conjunctival Staining
时间窗: Baseline to 84 days
Mean change from baseline at day 84 for the lissamine green conjunctival staining score in the designated study eye. The Investigator recorded a score for each area of each eye on a 0 (No punctate stain in zone) to 3 (Densely concentrated micropunctate stain spots) scale
Global Symptom Score
时间窗: Baseline to 84 days
Mean change from baseline at day 84 for the global symptom score. The freuency and severy of dry eye and irritation scores were used to calculate symptom score as follows: Frequency of dry eye/irritation based on a scale of 0 (rarely) to 100 (all the time) Severity of dryness or irritation based on a scale of 0 (very mildly) to 100 (very severe). The global symptom score was calculated as the square root of the frequency score times the severity score
次要结局
- Corneal Staining Score(Baseline to 84 days)
- Schirmer's Test(Baseline to 84 days)
- Patient Satisfaction(Baseline to 84 days)
- Tear Film Break up Time (TBUT)(Baseline to 84 days)