ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA
Condition: Age-related Macular Degeneration
MeSH terms: Macular Degeneration; Geographic Atrophy
Intervention: Subcutaneous elamipretide through the elamipretide delivery system; Subcutaneos placebo through the elamipretide delivery system
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 176.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: AMD; Macular degeneration; non-central geographic atrophy; MTP-131; elamipretide

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.
    

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.