Part A: a Prospective, Randomized, Double-masked, Vehicle Controlled, Paired-eye Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability and Efficacy of Elamipretide Topical Ophthalmic Solution in Subjects With Fuchs' Corneal Endothelial Dystrophy (FCED) Presenting With Mild to Moderate Corneal Edema Part B: a Prospective, Randomized, Double-masked, Vehicle Controlled, Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution in Subjects With FCED Presenting With Mild to Moderate Corneal Edema.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Incidence and Severity of Ocular TEAEs.
研究概览
简要总结
This is a Phase 1/2 prospective, randomized, double-masked, and vehicle-controlled trial in two parts to evaluate the safety, tolerability, and efficacy of elamipretide topical ophthalmic solution in patients with Fuchs' Corneal Endothelial Dystrophy (FCED) presenting with mild to moderate corneal edema.
详细描述
This is a Phase 1/2 trial in two parts. Part A is a prospective, randomized, double-masked, vehicle controlled, paired-eye study in approximately 16 subjects to evaluate safety, tolerability and efficacy of elamipretide 1.0% topical ophthalmic solution in patients with Fuchs' Corneal Endothelial Dystrophy (FCED) presenting with mild to moderate corneal edema. Part B is a prospective, randomized double-masked, vehicle controlled study in approximately 11 subjects to evaluate safety, tolerability, and efficacy of elamipretide 3.0% topical ophthalmic solution in patients with FCED presenting with mild to moderate corneal edema.
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
- •Adults ≥18 years old at the time of Screening Visit
- •Diagnosis of FCED OU (both eyes) based on clinical and ophthalmic test findings
- •Clinical evidence of corneal edema OU diagnosed with FCED, including one or more of the following signs: corneal epithelial microcysts, corneal epithelial bullae, stromal folds, or stromal haze
- •Central corneal thickness of 550 μm to 700 μm (inclusive) in at least one eye diagnosed with FCED, as measured by ultrasonic pachymetry at the time of Screening Visit and Baseline Visit
- •Best-corrected distance visual acuity (BCVA) of 20/25 to 20/320 (inclusive) at the time of Screening Visit and Baseline Visit OU
- •Women of childbearing potential must agree to use birth control as specified in the protocol from the date they sign the informed consent form (ICF) until after the last study
- •Able to give informed consent and willing to comply with all study visits and examinations
- •Part B only: The presence of central endothelium, as determined by the investigator, with an area of contiguous endothelial cells within 1 mm of the central cornea as measured by confocal laser scanning microscopy (CLSM) or specular microscopy at the time of Screening Visit
排除标准
- •Corneal findings of any type (including, but not limited to, stromal haze or stromal scarring), in either eye, that, based on investigator's assessment, limit the probability of visual improvement after corneal deturgescence
- •Any ocular pathology requiring treatment with topical ophthalmic drops, with the exception of glaucoma or ocular hypertension
- •Use of topical hypertonic saline drops for 3 days prior to Screening and throughout the duration of the study
- •History of corneal disease (other than FCED) or corneal surgery in either eye
- •Current use or likely need for the use of contact lens at any time during the study
- •History of previous corneal or anterior segment surgery such as LASIK, photorefractive keratectomy, endothelial keratoplasty, penetrating keratoplasty cataract surgery or glaucoma surgery.
- •Any disease or medical condition that in the opinion of the investigator would prevent the subject from participating in the study or might confound study results
- •Participation in other investigational drug or device clinical trials within 30 days prior to enrollment, or planning to participate in any other investigational drug or device clinical trials within 30 days of study completion
- •Women who are pregnant or lactating
- •Part B only: Participation in Part A of SPIFD-101
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Elamipretide 1.0% Ophthalmic Solution Part A (Cohort 1)
Part A Each subject will receive one drop of elamipretide 1.0% ophthalmic solution BID in the randomly selected study eye (Cohort 1).
干预措施: Part A Elamipretide 1.0% Ophthalmic Solution (Drug)
Elamipretide 3.0% Ophthalmic Solution Part B (Cohort 2)
Part B Each subject will receive one drop of elamipretide 3.0% ophthalmic solution BID in both the right and left study eyes (Cohort 2).
干预措施: Part B Elamipretide 3.0% Ophthalmic Solution (Drug)
Placebo A
Part A: Each subject will receive one drop of vehicle solution BID in the paired eye of the randomly selected study eye (Cohort 1).
干预措施: Part A Placebo (Drug)
Part B Placebo
Part B Each subject will receive one drop of vehicle solution BID in both the right and left study eyes (Cohort 2).
干预措施: Part B Placebo (Drug)
结局指标
主要结局
Incidence and Severity of Ocular TEAEs.
时间窗: Screening Visit, Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16
The incidence and severity of ocular treatment emergent adverse events (TEAEs)
The Incidence and Severity of Systemic Adverse Events
时间窗: Screening Visit, Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16
The incidence and severity of systemic treatment emergent adverse events (TEAEs)
Change From Baseline in Findings From Slit Lamp Examinations (SLE) Part A
时间窗: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16
Number of participants who had a change from baseline from normal or abnormal not clinically significant, to abnormal clinically significant (CS) findings for slit lamp examinations (SLE) for Part A. Part B is reported as separate outcome since unit of measure is number of eyes.
Change From Baseline in Findings From Slit Lamp Examinations (SLE) Part B
时间窗: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16
Number of eyes with a change from baseline from normal or abnormal not clinically significant, to abnormal clinically significant (CS) findings for slit lamp examinations (SLE) for Part B. Part A is reported as separate outcome.
Change From Baseline in Intraocular Pressure (IOP) for Part A
时间窗: Baseline, Week 1, Week 4, Week 8, Week 12
Change from Baseline in intraocular pressure (IOP) using Goldmann applanation tonometry for Part A
Change From Baseline in Intraocular Pressure (IOP) for Part B
时间窗: Baseline, Week 1, Week 4, Week 8, Week 12 , and Week 16 or early discontinuation visit
Change from Baseline in intraocular pressure (IOP) using Goldmann applanation tonometry for Part B. Part A is reported separately.
次要结局
- Change From Baseline in Central Corneal Thickness by Visit Part A as Measured by Pachymetry for Part A(Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16)
- Central Corneal Thickness Part B(Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16, or Early discontinuation visit)
- Change From Baseline Endothelial Cell Hexagonality in Percentage Over All 12 Weeks for Part A(Baseline, Week 1, 4, 8, and 12)
- Corneal Endothelial Cell Hexagonality Part B(Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16 or early discontinuation visit)
- Change From Baseline in Best Corrected Visual Acuity (BCVA) Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale for Part A.(Baseline, Weeks 1, 4, 8, 12, and 16)
- Best Corrected Visual Acuity (BCVA) Score Using ETDRS Scale for Part B(Baseline, Weeks 1, 4, 8, 12, and 16)
- Change From Baseline in Endothelial Cell Density Over All 12 Weeks for Part A(Baseline, Weeks 1, 4, 8, and 12)
- Corneal Endothelial Cell Density Part B(Baseline, Weeks 1, 4, 8, 12, and 16.)
- Change From Baseline in Endothelial Cell Coefficient of Variation Over All 12 Weeks for Part A(Baseline, Week 12)
- Coefficient of Variation (CoV) Part B(Baseline, Weeks 1, 4, 8,12, and 16)
- Change From Baseline in Corneal Area Affected by Microcysts for Part A(Baseline, Weeks 1, 4, 8, 12, and 16)
- Corneal Area Affected by Microcysts: Part B(Baseline, Weeks 1, 4, 8, 12, and 16, or early discontinuation visit)
- Change From Baseline in Corneal Bullae for Part A.(Baseline, Week 1, Week 4, Week 8, Week 12, Week 16)
- Corneal Bullae: Part B(Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, or early discontinuation visit)
- Change From Baseline in Severity of Corneal Stromal Folds for Part A(Baseline, Weeks 1, 4, 8, 12, and 16)
- Severity of Corneal Stromal Folds:Part B(Baseline, Week 1, 4, 8, 12, and 16, or early discontinuation visit)
- Change From Baseline in Contrast Sensitivity (Log Score) for Part A(Baseline, Week 1, 4, 8, 12 weeks)
- Contrast Sensitivity for Part B; By-subject Data(Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, or early discontinuation visit)