Clinical trial NCT02653391: A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for the Treatment of Fuchs' Corneal Endothelial Dystrophy (FCED)
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Fuchs' Corneal Endothelial Dystrophy (FCED)
Keywords: Fuchs' Corneal Endothelial Dystrophy
FCED
Ocuvia™
MTP-131
Lead sponsor: Stealth BioTherapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-12
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Incidence and Severity of Ocular TEAEs.
timeFrame: Screening Visit, Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16
measure: The Incidence and Severity of Systemic Adverse Events
timeFrame: Screening Visit, Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16
measure: Change From Baseline in Findings From Slit Lamp Examinations (SLE) Part A
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16
measure: Change From Baseline in Findings From Slit Lamp Examinations (SLE) Part B
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16
measure: Change From Baseline in Intraocular Pressure (IOP) for Part A
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12
measure: Change From Baseline in Intraocular Pressure (IOP) for Part B
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12 , and Week 16 or early discontinuation visit
Secondary outcomes:
measure: Change From Baseline in Central Corneal Thickness by Visit Part A as Measured by Pachymetry for Part A
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16
measure: Central Corneal Thickness Part B
timeFrame: Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16, or Early discontinuation visit
measure: Change From Baseline Endothelial Cell Hexagonality in Percentage Over All 12 Weeks for Part A
timeFrame: Baseline, Week 1, 4, 8, and 12
measure: Corneal Endothelial Cell Hexagonality Part B
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16 or early discontinuation visit
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA) Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale for Part A.
timeFrame: Baseline, Weeks 1, 4, 8, 12, and 16
measure: Best Corrected Visual Acuity (BCVA) Score Using ETDRS Scale for Part B
timeFrame: Baseline, Weeks 1, 4, 8, 12, and 16
measure: Change From Baseline in Endothelial Cell Density Over All 12 Weeks for Part A
timeFrame: Baseline, Weeks 1, 4, 8, and 12
measure: Corneal Endothelial Cell Density Part B
timeFrame: Baseline, Weeks 1, 4, 8, 12, and 16.
measure: Change From Baseline in Endothelial Cell Coefficient of Variation Over All 12 Weeks for Part A
timeFrame: Baseline, Week 12
measure: Coefficient of Variation (CoV) Part B
timeFrame: Baseline, Weeks 1, 4, 8,12, and 16
measure: Change From Baseline in Corneal Area Affected by Microcysts for Part A
timeFrame: Baseline, Weeks 1, 4, 8, 12, and 16
measure: Corneal Area Affected by Microcysts: Part B
timeFrame: Baseline, Weeks 1, 4, 8, 12, and 16, or early discontinuation visit
measure: Change From Baseline in Corneal Bullae for Part A.
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16
measure: Corneal Bullae: Part B
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, or early discontinuation visit
measure: Change From Baseline in Severity of Corneal Stromal Folds for Part A
timeFrame: Baseline, Weeks 1, 4, 8, 12, and 16
measure: Severity of Corneal Stromal Folds:Part B
timeFrame: Baseline, Week 1, 4, 8, 12, and 16, or early discontinuation visit
measure: Change From Baseline in Contrast Sensitivity (Log Score) for Part A
timeFrame: Baseline, Week 1, 4, 8, 12 weeks
measure: Contrast Sensitivity for Part B; By-subject Data
timeFrame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, or early discontinuation visit
Other outcomes:
Locations:
city: Edgewood
country: United States
facility: Cincinnati Eye Institute
state: Kentucky
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
Study officials:
affiliation: Ophthalmic Consultants of Boston
name: Michael Raizman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cincinnati Eye Institute
name: Edward Holland, MD
role: PRINCIPAL_INVESTIGATOR
References: