A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for the Treatment of Fuchs' Corneal Endothelial Dystrophy (FCED) (SPIFD-101)

• ClinicalTrials.gov Identifier: NCT02653391
• Recruitment Status: Completed
• First Posted: January 12, 2016
• Results First Posted: September 17, 2021
• Last Update Posted: September 17, 2021
• Sponsor: Stealth BioTherapeutics Inc.
• Information provided by (Responsible Party): Stealth BioTherapeutics Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Fuchs' Corneal Endothelial Dystrophy (FCED)	Drug: Part A Elamipretide 1.0% Ophthalmic Solution; Drug: Part B Elamipretide 3.0% Ophthalmic Solution; Drug: Part A Placebo; Drug: Part B Placebo	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: February 2016
• Actual Primary Completion Date: March 2018
• Actual Study Completion Date: December 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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).	Drug: Part A Elamipretide 1.0% Ophthalmic Solution; Part A Each subject will receive one drop of elamipretide 1.0% ophthalmic solution BID in the randomly selected study eye.; Other Name: MTP-131, Bendavia
Experimental: 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).	Drug: Part B Elamipretide 3.0% Ophthalmic Solution; Part B Each subject will receive one drop of elamipretide 3.0% ophthalmic solution BID in both eyes.; Other Name: MTP-131, Bendavia
Placebo Comparator: 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).	Drug: Part A Placebo; Part A Each subject will receive one drop of vehicle ophthalmic solution BID in the paired eye of the randomly selected study eye.
Placebo Comparator: 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).	Drug: Part B Placebo; Part B: Each subject will receive one drop of vehicle ophthalmic solution BID in both eyes.

Outcome Measures

Primary Outcome Measures :

1. Incidence and Severity of Ocular TEAEs. [ Time Frame: 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)
2. The Incidence and Severity of Systemic Adverse Events [ Time Frame: 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)
3. Change From Baseline in Findings From Slit Lamp Examinations (SLE) Part A [ Time Frame: 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.
4. Change From Baseline in Findings From Slit Lamp Examinations (SLE) Part B [ Time Frame: 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.
5. Change From Baseline in Intraocular Pressure (IOP) for Part A [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12 ]
   Change from Baseline in intraocular pressure (IOP) using Goldmann applanation tonometry for Part A
6. Change From Baseline in Intraocular Pressure (IOP) for Part B [ Time Frame: 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.

Secondary Outcome Measures :

1. Change From Baseline in Central Corneal Thickness by Visit Part A as Measured by Pachymetry for Part A [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16 ]
   Change from Baseline in Central Corneal Thickness by Visit as measured by Pachymetry for Part A. Part B is reported as a separate outcome measure.
2. Central Corneal Thickness Part B [ Time Frame: Baseline (Day 1), Week 1, Week 4, Week 8, Week 12, and Week 16, or Early discontinuation visit ]
   Central Corneal Thickness: by-subject data as measured by Pachymetry and Pentacam. Part A is reported as a separate outcome measure.
3. Change From Baseline Endothelial Cell Hexagonality in Percentage Over All 12 Weeks for Part A [ Time Frame: Baseline, Week 1, 4, 8, and 12 ]
   Change From Baseline in Endothelial Cell Hexagonality in Percentage Over All 12 Weeks for Part A. Specular microscopy is a noninvasive photographic technique that allows visualization and analyzation the corneal endothelium. Using computer-assisted morphometry, specular microscopes analyzes the size, shape and population of the endothelial cells. Histologically, healthy corneal cells initially have a hexagonal shape. As endothelial cells die, neighboring cells enlarge to cover the empty space once occupied by the cell. This, in turn, causes the remaining cells to lose their hexagonal shape. Assessments were performed using the flex center and full auto methods for Part A and data from the flex center method was summarized. The flex center method was used for Part B. The percent of Part B is entered as a separate outcome measure. A decrease from baseline in % cell hexagonality means worse outcome, a increase from baseline means better outcome.
4. Corneal Endothelial Cell Hexagonality Part B [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, and Week 16 or early discontinuation visit ]
   Corneal Endothelial Cell Hexagonality in Percentage by-subject data: Part B. Data was only listed in weeks where images were good enough quality to quantify. Specular microscopy is a noninvasive photographic technique that allows visualization and analyzation the corneal endothelium. Using computer-assisted morphometry, specular microscopes analyzes the size, shape and population of the endothelial cells. Histologically, healthy corneal cells initially have a hexagonal shape. As endothelial cells die, neighboring cells enlarge to cover the empty space once occupied by the cell. This, in turn, causes the remaining cells to lose their hexagonal shape. The flex center method was used for Part B. A decrease in percent of cell hexagonality from baseline means worse outcome, an increase from baseline means better outcome.
5. Change From Baseline in Best Corrected Visual Acuity (BCVA) Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Scale for Part A. [ Time Frame: Baseline, Weeks 1, 4, 8, 12, and 16 ]
   Best corrected visual acuity (BCVA) using the using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale by visit. ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome). Part B was listed separately.
6. Best Corrected Visual Acuity (BCVA) Score Using ETDRS Scale for Part B [ Time Frame: Baseline, Weeks 1, 4, 8, 12, and 16 ]
   Best corrected visual acuity (BCVA) using the using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale by visit. ETDRS charts present a series of five letters of equal difficulty on each row, with standardized spacing between letters and rows; there is a total of 14 lines (70 letters), with letter size increasing further geometrically and equivalently in every line by a factor of 1.2589 (or 0.1 log unit), moving up the chart. Minimum score of zero, maximum score of 100. Change from baseline: a more negative score is worse outcome, a more positive score is better outcome. A lower score means less letters were read correctly (worse outcome) and a higher score means more letters were read correctly (better outcome).
7. Change From Baseline in Endothelial Cell Density Over All 12 Weeks for Part A [ Time Frame: Baseline, Weeks 1, 4, 8, and 12 ]
   Change From Baseline in Endothelial Cell Counts, or density (Counts/mm^2) over all 12 weeks for Part A. Part B is entered as a separate outcome measure.
8. Corneal Endothelial Cell Density Part B [ Time Frame: Baseline, Weeks 1, 4, 8, 12, and 16. ]
   Corneal Endothelial Cell Density: Part B, By-subject data for all time points where images were readable. For all time points where there were "Poor Quality Images" or "too few cells to register", there were no data available, and these were not listed below.
9. Change From Baseline in Endothelial Cell Coefficient of Variation Over All 12 Weeks for Part A [ Time Frame: Baseline, Week 12 ]
   Change From Baseline in Endothelial Cell Coefficient of Variation Over All 12 Weeks. Coefficient of variation (CV) is Standard deviation (SD) of cell area divided by the mean cell area of endothelial cell analyzed. CV represents the coefficient, or degree, of variation in the sizes of the endothelial cells (polymegethism). By measuring the variation in size between endothelial cells, the system can measure how much cell loss is occurring. The more variation, the worse the outcome. Part B is is entered as a separate outcome measure.
10. Coefficient of Variation (CoV) Part B [ Time Frame: Baseline, Weeks 1, 4, 8,12, and 16 ]
    Part B, By-subject data for all time points where images were readable. For all time points where there were "Poor Quality Images" or "too few cells to register" there were no data available. CoV represents the coefficient, or degree, of variation in the sizes of the endothelial cells. By measuring the variation in size between endothelial cells, the system can measure how much cell loss is occurring. A CoV less than 40 is normal.
11. Change From Baseline in Corneal Area Affected by Microcysts for Part A [ Time Frame: Baseline, Weeks 1, 4, 8, 12, and 16 ]
    Change from Baseline in corneal area affected by microcysts by visit for Part A.
12. Corneal Area Affected by Microcysts: Part B [ Time Frame: Baseline, Weeks 1, 4, 8, 12, and 16, or early discontinuation visit ]
    Corneal area affected by microcysts: by-subject data for Part B. No microcysts were present for any timepoints.
13. Change From Baseline in Corneal Bullae for Part A. [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16 ]
    Count of participants in number, size and location of bullae by treatment. Part B is listed separately.
14. Corneal Bullae: Part B [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, or early discontinuation visit ]
    Number, size and location of Corneal bullae: By-subject data: Part B.
15. Change From Baseline in Severity of Corneal Stromal Folds for Part A [ Time Frame: Baseline, Weeks 1, 4, 8, 12, and 16 ]
    Change from baseline in severity of corneal stromal folds by visit. Descriptive assessment made by Investigator; severity is not assessed using a scale.
16. Severity of Corneal Stromal Folds:Part B [ Time Frame: Baseline, Week 1, 4, 8, 12, and 16, or early discontinuation visit ]
    Severity of corneal stromal folds by-subject data by visit. Descriptive assessment made by Investigator in the following categories: Not present, trace, mild.
17. Change From Baseline in Contrast Sensitivity (Log Score) for Part A [ Time Frame: Baseline, Week 1, 4, 8, 12 weeks ]
    Change from Baseline in contrast sensitivity over all 12 weeks log score at 3, 6, 12, 18 cycles per degree (cpd) using Vector Vision's CSV-1000E. Standard tables for the VectorVision's CSV-1000E model were used to convert linear results to the log values. Lower log scores equals lower contrast sensitivity and worse outcome. Higher log scores mean higher contrast sensitivity and better outcome. For 3cpd, range is 0.7-2.08; 6 cpd: 0.91-2.29; 12 cpd: 0.61-1.99; 18cpd: 0.17-1.55, unless no gratings were visible. If no gratings were visible, .3 log was subtracted from the lowest score for 3, 6, and 12cpd. For 18cpd .01 log was used, or essentially 100% contrast.
18. Contrast Sensitivity for Part B; By-subject Data [ Time Frame: Baseline, Week 1, Week 4, Week 8, Week 12, Week 16, or early discontinuation visit ]
    Contrast Sensitivity log score at 3, 6, 12, 18 cycles per degree (cpd) using Vector Vision's CSV-1000E by-subject data, Part B. Part A is listed separately. Standard tables for the VectorVision's CSV-1000E model were used to convert linear results to the log values. Lower log scores equals lower contrast sensitivity and worse outcome. Higher log scores mean higher contrast sensitivity and better outcome. For 3cpd, range is 0.7-2.08; 6 cpd: 0.91-2.29; 12 cpd: 0.61-1.99; 18cpd: 0.17-1.55, unless no gratings were visible. If no gratings were visible, .3 log was subtracted from the lowest score for 3, 6, and 12cpd. For 18cpd .01 log was used, or essentially 100% contrast.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Kentucky

Cincinnati Eye Institute

Edgewood, Kentucky, United States, 41017

United States, Massachusetts

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Stealth BioTherapeutics Inc.

Investigators

• Principal Investigator: Michael Raizman, MD; Ophthalmic Consultants of Boston
• Principal Investigator: Edward Holland, MD; Cincinnati Eye Institute

  Study Documents (Full-Text)

Documents provided by Stealth BioTherapeutics Inc.:

Study Protocol and Statistical Analysis Plan  [PDF] August 18, 2015

More Information

• Responsible Party: Stealth BioTherapeutics Inc.
• ClinicalTrials.gov Identifier: NCT02653391
• Other Study ID Numbers: SPIFD-101
• First Posted: January 12, 2016
• Results First Posted: September 17, 2021
• Last Update Posted: September 17, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Stealth BioTherapeutics Inc.:

Fuchs' Corneal Endothelial Dystrophy; FCED; Ocuvia™; MTP-131

Additional relevant MeSH terms:

Corneal Dystrophies, Hereditary; Corneal Diseases; Eye Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Pharmaceutical Solutions; Ophthalmic Solutions