A Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration
Condition: Geographic Atrophy
MeSH terms: Macular Degeneration; Geographic Atrophy; Atrophy
Intervention: APL-2; APL-2; Sham Procedure; Sham Procedure
Intervention description: Complement (C3) Inhibitor; Complement (C3) Inhibitor; Subjects will receive a Sham procedure every month; Subjects will receive a Sham procedure every other month
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 637.0
Sex: All
Minimum age: 60 Years
Healthy volunteers: No

Summary:

      This is a 24-month, Phase III, multicenter, randomized, double-masked, sham-injection
      controlled study to assess the efficacy and safety of multiple IVT injections of APL-2 in
      subjects with GA secondary to AMD.
    

Eligibility criteria:

        Inclusion Criteria:

        The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria,
        the eye with the worst visual acuity at the screening visit will be designated as the study
        eye. If both eyes have the same visual acuity, the right eye will be selected as the study
        eye.

        Ocular- specific inclusion criteria apply to the study eye only, unless otherwise
        specified.

          -  Age ≥ 60 years.

          -  Normal Luminance best corrected visual acuity of 24 letters or better using Early
             Treatment Diabetic Retinopathy Study (ETDRS) charts (approximately 20/320 Snellen
             equivalent).

          -  Clinical diagnosis of GA of the macula secondary to AMD as determined by the
             Investigator and confirmed by the Reading Center.

          -  The GA lesion must meet the following criteria as determined by the central reading
             center's assessment of Fundus Autofluorescence (FAF) imaging at screening:

               -  Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas [DA] respectively)

               -  If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA), with
                  the overall aggregate area of GA, as specified above in 4a.

               -  The entire GA lesion must be completely visualized on the macula centered image
                  and must be able to be imaged in its entirety and not contiguous with any areas
                  of peripapillary atrophy.

               -  Presence of any pattern of hyperautofluorescence in the junctional zone of GA.
                  Absence of hyperautofluorescence (i.e. pattern = none) is exclusionary.

          -  Adequate clarity of ocular media, adequate pupillary dilation, and fixation to permit
             the collection of good quality images as determined by the Investigator.

          -  Meets the following criteria related to microperimetry:

               -  Able to detect fixation target.

               -  Total elapsed time to complete the 10-2 68 point exam is ≤ 30 minutes in
                  duration.

               -  Reliability test ratio must be ≤ 20%.

               -  Subject is willing and able to undertake microperimetry assessment in the opinion
                  of the investigator.

          -  Female subjects must be:

               -  Women of non-child-bearing potential (WONCBP), or

               -  Women of child-bearing potential (WOCBP) with a negative pregnancy test at
                  screening and must agree to use protocol defined methods of contraception for the
                  duration of the study and refrain from breastfeeding for the duration of the
                  study.

          -  Males with female partners of child-bearing potential must agree to use protocol
             defined methods of contraception and agree to refrain from donating sperm for the
             duration of the study.

          -  Willing and able to give informed consent and to comply with the study procedures and
             assessments.

        Exclusion Criteria:

        Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.

          -  GA secondary to a condition other than AMD such as Stargardt disease, cone rod
             dystrophy or toxic maculopathies like plaquenil maculopathy in either eye.

          -  Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or
             an axial length >26 mm.

          -  Any history or active choroidal neovascularization (CNV), associated with AMD or any
             other cause, including any evidence of retinal pigment epithelium rips or evidence of
             neovascularization anywhere based on SD-OCT imaging and/or fluorescein angiography as
             assessed by the Reading Center.

          -  Presence of an active ocular disease that in the opinion of the Investigator
             compromises or confounds visual function, including but not limited to, uveitis, other
             macular diseases (e.g. clinically significant epiretinal membrane (ERM), full
             thickness macular hole or uncontrolled glaucoma/ocular hypertension. Benign conditions
             in the opinion of the investigator such as peripheral retina dystrophy are not
             exclusionary).

          -  Intraocular surgery (including lens replacement surgery) within 3 months prior to
             randomization.

          -  History of laser therapy in the macular region.

          -  Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for
             posterior capsule opacification done at least 60 days prior to screening is not
             exclusionary.

          -  Any ocular condition other than GA secondary to AMD that may require surgery or
             medical intervention during the study period or, in the opinion of the Investigator,
             could compromise visual function during the study period.

          -  Any contraindication to IVT injection including current ocular or periocular
             infection.

          -  History of prior intravitreal injection.

          -  Unable to perform microperimetry reliably in the opinion of the investigator

          -  Prior participation in another interventional clinical study for intravitreal
             therapies in either eye (including subjects receiving sham).

          -  Prior participation in another interventional clinical study for geographic atrophy in
             either eye including investigational oral medication and placebo.

          -  Participation in any systemic experimental treatment or any other systemic
             investigational new drug within 6 weeks or 5 half-lives of the active ingredient
             (whichever is longer) prior to the start of study treatment. Note: clinical trials
             solely involving observation, over-the-counter vitamins, supplements, or diets are not
             exclusionary.

          -  Medical or psychiatric conditions that, in the opinion of the investigator, make
             consistent follow-up over the 24-month treatment period unlikely, or would make the
             subject an unsafe study candidate.

          -  Any screening laboratory value (hematology, serum chemistry or urinalysis) that in the
             opinion of the Investigator is clinically significant and not suitable for study
             participation.

          -  Known hypersensitivity to fluorescein sodium for injection or hypersensitivity to
             APL-2 or any of the excipients in APL-2 solution.