ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA

Age-related Macular Degeneration Clinical Trial

— ReCLAIM-2  

Official title:

A Phase 2 Randomized, Double-Masked, Placebo-Controlled Clinical Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Elamipretide in Subjects With Age-Related Macular Degeneration With Non-central Geographic Atrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03891875
• Other study ID #: SPIAM-202
• Status: Completed
• Phase: Phase 2
• Start date: March 27, 2019
• Est. completion date: April 14, 2022

Study information

• Verified date: October 2023
• Source: Stealth BioTherapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, double-masked, placebo-controlled study to evaluate the safety, efficacy and pharmacokinetics of elamipretide in subjects with Age-Related Macular Degeneration with non-central Geographic Atrophy.

Description:

This was a randomized, double-masked, placebo controlled study using three periods to evaluate the safety, efficacy and pharmacokinetics of elamipretide in subjects with Age-Related Macular Degeneration with non-central Geographic Atrophy. The total duration of subject participation was up to 54 weeks, including a Screening Period (≤2 weeks), Treatment Period (48 weeks), and Follow-up (4 weeks). 176 eligible subjects were randomized in a 2:1 ratio (elamipretide:placebo) to receive 40 mg elamipretide or placebo. The study drug (i.e., elamipretide or placebo) was administered daily via SC injection using the elamipretide delivery system during the 48 week Treatment Period. After completion of the 48-week Treatment Period subjects continued to be monitored for safety during the 4-week Follow-up Period and an end of study (EOS) Follow-up Visit was conducted at Week 52.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 176
• Est. completion date: April 14, 2022
• Est. primary completion date: February 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

• Adults = 55 years of age with at least 1 eye with AMD with non-central GA as determined by FAF.

Ocular conditions-study eye

• GA in the study eye at the Screening Visit may be multi-focal, but the cumulative GA lesion and size must:

1. be = 0.05 mm2 and = 10.16 mm2 and

2. reside completely within the FAF 30 or 35 degree image.

3. must be at least 150 µm from foveal center with preserved outer retinal structural details

• No evidence of CNV by history, OCT or FA in the study eye.

• BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) score of = 55 letters (Snellen equivalent = 20/70) in the study eye at the Screening Visit and Baseline Visit.

• LL BCVA by ETDRS score of = 10 letters in the study eye at the Screening Visit and Baseline Visit.

• LL VA deficit (defined as difference the between BCVA and LL BCVA) of > 5 letters in the study eye at Screening and Baseline Visits.

• The fellow eye may have any of the following: no AMD, AMD without GA, AMD with GA, CNV AMD, or central GA. Ongoing treatment with anti-angiogenic therapies in the fellow eye is allowable.

• Sufficiently clear ocular media, adequate pupillary dilation, fixation to permit quality fundus imaging, and ability to cooperate sufficiently for adequate ophthalmic visual function testing and anatomic assessment in the study eye.

Systemic and general criteria

Exclusion Criteria:

Ocular conditions-study eye

• The absence of observable hyper-FAF at the margins of the GA in the study eye(only for lesions = 0.25mm2)

• Atrophic retinal disease of causality other than AMD including myopia-related maculopathy and monogenetic macular dystrophies including pattern dystrophy and adult-onset Stargardt disease in the study eye.

• Presence or diagnosis of exudative AMD or CNV in the study eye.

• Presence of retinal vein occlusion in the study eye.

• Presence of diabetic retinopathy (a history of diabetes mellitus without retinopathy is not a criterion for exclusion) in either eye.

• Presence of vitreous hemorrhage in the study eye.

• History of retinal detachment in the study eye.

• History of macular hole (stages 2 to 4) in the study eye.

• Presence of an epiretinal membrane that causes distortion of the retinal contour in the study eye.

• Presence of vitreomacular traction in the study eye.

• At the Screening Visit, advanced glaucoma resulting in a cup to disc ratio of > 0.8 in the study eye.

• History of glaucoma filtration surgery or uncontrolled glaucoma defined as IOP > 22 mmHg at baseline despite anti-glaucoma treatment with or without topical anti-hypertensive eye drops in the study eye OR currently using > 2 medications (note: combination medications count as 2 medications).

• Presence of visually significant cataract OR presence of significant posterior capsular opacity in the setting of pseudophakia. Significant cataract is defined as > +2 nuclear sclerosis based upon the scale below or any Posterior Subcapsular Cataract in the study eye. The Sponsor, or its designee, will supply the trial sites with a copy of the standard photographs.

• Presence of significant keratopathy or any other media or corneal opacity that would cause scattering of light or alter visual function, especially in LL conditions in the study eye.

• Ocular incisional or laser surgery (including cataract surgery) in the study eye within 90 days before Day 1.

• Yag laser capsulotomy in the study eye within 30 days before Day 1.

• Aphakia in the study eye.

• History of vitrectomy surgery, submacular surgery, or any vitreoretinal surgery in the study eye.

• Prior treatment with Visudyne® (verteporfin) ocular photodynamic therapy, external-beam radiation therapy (for intraocular conditions), or transpupillary thermotherapy in the study eye.

• History of subthreshold laser treatment or other forms of photobiomodulation for AMD in the study eye.

• Intravitreal drug delivery in the past 60 days or 5-half-lives of the injected drug whichever is longer (e.g., intravitreal corticosteroid injection, anti angiogenic drugs, or device implantation) in the study eye.

• Current use of medications known to be toxic to the lens, retina, or optic nerve (e.g., deferoxamine, chloroquine/hydroxychloroquine [Plaquenil®], tamoxifen, phenothiazines, ethambutol, digoxin, and aminoglycosides) from the Screening Visit through the completion of the trial.

Ocular conditions--either eye

• History of herpetic infection in either eye.

• Concurrent disease in either the study eye or fellow control eye that could require medical or surgical intervention during the study period.

• Active uveitis and/or vitritis (grade trace or above) in either eye.

• History of idiopathic or autoimmune-associated uveitis in either eye.

• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.

Systemic conditions.

• Known to be immunocompromised or receiving systemic immunosuppression for = 4 consecutive weeks prior to screening.

• Any disease or medical condition that in the opinion of the Investigator would prevent the subject from successfully participating in the study or might confound study results.

General

• Participation in other investigational drug or device clinical studies within 30 days of enrollment and/or planning to participate in any other investigational drug or device clinical studies within 30 days of study completion.

• History of allergy to fluorescein that is not amenable to treatment.

• Creatinine clearance of = 30 mL/min at the Screening Visit (using Modification of Diet in Renal Disease Study formula).

• Inability to comply with study or follow-up procedures.

• Inability to obtain color fundus photograph, FAF, and FA of sufficient quality to be analyzed and interpreted.

• Active malignancy or any other cancer from which the subject has been cancer-free for < 2 years.

• History of allergic reaction to the investigational drug or any of its components.

• Prior treatment with Elamipretide.

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Geographic Atrophy
• Macular Degeneration

Intervention

Combination Product:
• Subcutaneous elamipretide through the elamipretide delivery system
Subjects will be randomized in a 2:1 ratio to receive either elamipretide or placebo through the elamipretide delivery system. Subjects will dose daily for up to 48 weeks.
• Subcutaneos placebo through the elamipretide delivery system
Subjects will be randomized in a 2:1 ratio to receive either elamipretide or placebo through the elamipretide delivery system. Subjects will dose daily for up to 48 weeks.

Locations

Country	Name	City	State
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Southeast Retina Center, PC	Augusta	Georgia
United States	Retina Research Center, PLLC	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina-Vitreous Associates Medical Group	Beverly Hills	California
United States	Retina Center of New Jersey LLC	Bloomfield	New Jersey
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	University of Virginia, Department of Ophthalmology	Charlottesville	Virginia
United States	Sterling Research Group	Cincinnati	Ohio
United States	Duke Eye center	Durham	North Carolina
United States	Ophthalmology Associates	Fort Worth	Texas
United States	Texas Retina Associates	Fort Worth	Texas
United States	Cumberland valley retina consultants	Hagerstown	Maryland
United States	Retina Consultants of Houston, PA	Houston	Texas
United States	Specialty Eye Institute	Jackson	Michigan
United States	Retina Consultants of Houston	Katy	Texas
United States	Valley Retina Institute, PA	McAllen	Texas
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	MedEye Associates	Miami	Florida
United States	Tennessee Retina	Nashville	Tennessee
United States	Oklahoma University Health Sciences Center	Oklahoma City	Oklahoma
United States	Bascom Palmer Eye Institute	Palm Beach Gardens	Florida
United States	Retina Institute of California Medical Group	Palm Desert	California
United States	Associated Retina Consultants, Ltd.	Peoria	Arizona
United States	Arizona Retina & Vitreous Consultants	Phoenix	Arizona
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Retinal Research Institute, LLC	Phoenix	Arizona
United States	Retina Northwest, P.C	Portland	Oregon
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Retina Associates of Western New York	Rochester	New York
United States	California Retina Consultants	Santa Barbara	California
United States	California Retina Consultants	Santa Maria	California
United States	Global Retina Institute	Scottsdale	Arizona
United States	New England Retina Consultants	Springfield	Massachusetts
United States	New Jersey Retina	Teaneck	New Jersey
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Stealth BioTherapeutics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Macular Percentage of Ellipsoid Zone (EZ) Total Attenuation From Baseline	Change from Baseline in Macular Percentage of EZ Total Attenuation by OCT: Week 24 and Week 48 measures photoreceptor loss marked by EZ degradation. Lower increase in percentage means a better outcome. Higher increase in percentage means a worse outcome.	Baseline, Week 24 and Week 48
Primary	LL BCVA Score Change From Baseline	Change in low luminance best corrected visual acuity (LL BCVA) score from Baseline to the end of treatment (EOT; Week 48) assessment measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. 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).	Baseline and Weeks 4, 8, 12, 24, 36, 48
Primary	GA Area Change From Baseline by OCT	Geographic atrophy (GA) area: change from baseline as measured by optical coherence tomography (OCT) from Baseline to the end of treatment (EOT; Week 48)	Baseline and Weeks 12, 24, 36, 48
Secondary	LL RA Change From Baseline	Low-luminance ready acuity (LL RA) score change from baseline to the EOT (Week 48). Mean Critical Print Size with Low Luminance in Weeks 4, 12, 36, 48 as measured by the Logarithm of the Minimum Angle of Resolution LogMAR chart. Scores range from -0.3 to 1.0, where higher number means worse acuity/worse outcome, a lower number means better acuity/better outcome.	Baseline and Weeks 4,12, 36, 48
Secondary	BCVA Change From Baseline	Best-corrected visual acuity (BCVA) change from Baseline Change in best corrected visual acuity (BCVA) score from Baseline to the end of treatment (EOT; Week 48) assessment measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. 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).	Baseline and Weeks 4, 8, 12, 24, 36, 48
Secondary	GA Area as Measured by Fundus Autofluorescence (FAF) Change From Baseline	Change from Baseline in Mean Area of Geographic Atrophy (GA) by Fundus Autofluorescence (FAF) at Week 24. Fluorescein angiography (FA) was used to examine the circulation of the retina and choroid using fluorescein dye and a specialized camera to trace the dye. Fundus autofluorescence imaging of the retinal pigment epithelium and neurosensory retina was performed within 14 days of Day 0 and at every visit with the exception of Day 0 and Day 7. Atrophy is characterized by loss of the retinal pigment epithelium (RPE), overlying photoreceptors and underlying choriocapillaris. Greater area affected means a worse outcome than smaller area affected.	Baseline and Weeks 12, 24, 36, 48