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

NCT ID: NCT03891875

Last Updated: 2024-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-27
• Study Completion Date: 2022-04-14

Brief 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.

Detailed 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 once 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.

Conditions

Age-related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Elamipretide

Once daily 40 mg subcutaneous injection of elamipretide using the elamipretide delivery system for 48 weeks followed by a 4 week follow-up period.

Group Type: EXPERIMENTAL

Subcutaneous elamipretide through the elamipretide delivery system

Intervention Type: COMBINATION_PRODUCT

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.

Placebo

Once daily subcutaneous injection of placebo using the elamipretide delivery system for 48 weeks followed by a 4 week follow-up period.

Group Type: PLACEBO_COMPARATOR

Subcutaneos placebo through the elamipretide delivery system

Intervention Type: COMBINATION_PRODUCT

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.

Interventions

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.

Intervention Type: COMBINATION_PRODUCT

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.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

elamipretide; MTP-131; Bendavia

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stealth BioTherapeutics Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sathyanarayana

Role: STUDY_DIRECTOR

Stealth BioTherapeutics

Locations

Associated Retina Consultants, Ltd.

Peoria, Arizona, United States

Retinal Research Institute, LLC

Phoenix, Arizona, United States

Arizona Retina & Vitreous Consultants

Phoenix, Arizona, United States

Retinal Research Institute, LLC

Phoenix, Arizona, United States

Global Retina Institute

Scottsdale, Arizona, United States

California Retina Consultants

Bakersfield, California, United States

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States

Retina Institute of California Medical Group

Palm Desert, California, United States

California Retina Consultants

Santa Barbara, California, United States

California Retina Consultants

Santa Maria, California, United States

Bascom Palmer Eye Institute

Miami, Florida, United States

MedEye Associates

Miami, Florida, United States

Bascom Palmer Eye Institute

Palm Beach Gardens, Florida, United States

Center for Retina and Macular Disease

Winter Haven, Florida, United States

Southeast Retina Center, PC

Augusta, Georgia, United States

The Retina Care Center

Baltimore, Maryland, United States

Cumberland valley retina consultants

Hagerstown, Maryland, United States

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

New England Retina Consultants

Springfield, Massachusetts, United States

Specialty Eye Institute

Jackson, Michigan, United States

Retina Center of New Jersey LLC

Bloomfield, New Jersey, United States

New Jersey Retina

Teaneck, New Jersey, United States

Retina Associates of Western New York

Rochester, New York, United States

Duke Eye center

Durham, North Carolina, United States

Sterling Research Group

Cincinnati, Ohio, United States

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, United States

Retina Northwest, P.C

Portland, Oregon, United States

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States

Tennessee Retina

Nashville, Tennessee, United States

Retina Research Institute of Texas

Abilene, Texas, United States

Retina Research Center, PLLC

Austin, Texas, United States

Ophthalmology Associates

Fort Worth, Texas, United States

Texas Retina Associates

Fort Worth, Texas, United States

Retina Consultants of Houston, PA

Houston, Texas, United States

Retina Consultants of Houston

Katy, Texas, United States

Valley Retina Institute, PA

McAllen, Texas, United States

University of Virginia, Department of Ophthalmology

Charlottesville, Virginia, United States

Countries

United States

References

Ehlers JP, Hu A, Boyer D, Cousins SW, Waheed NK, Rosenfeld PJ, Brown D, Kaiser PK, Abbruscato A, Gao G, Heier J; ReCLAIM-2 (SPIAM-202) Study Investigators. ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. Ophthalmol Sci. 2024 Oct 9;5(1):100628. doi: 10.1016/j.xops.2024.100628. eCollection 2025 Jan-Feb.

Reference Type: DERIVED

PMID: 39605874 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SPIAM-202

Identifier Type: -

Identifier Source: org_study_id