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

A Phase 3, Multi-Center, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

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.

Study Overview

• Status: Completed
• Conditions: Geographic Atrophy
• Intervention / Treatment: Drug: APL-2; Other: Sham Procedure; Other: Sham Procedure

• Study Type: Interventional
• Enrollment (Actual): 637
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Strathfield, Australia, 2135
    • Strathfield Retina Clinic
  • Westmead, Australia, 2145
    • Sydney West Retina
  • New South Wales
    • Parramatta, New South Wales, Australia, 2150
      • Marsden Eye Specialist
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Adelaide Eye & Retina Clinic
  • South Block
    • Sydney, South Block, Australia, 2000
      • Save Sight Institute
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Lions Eye Institute
• Brazil
  • São Paulo, Brazil, 04021-001
    • UNIFESP - Federal University
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • UHN Toronto Western Hospital
• Czechia
  • Praha, Czechia, 150 00
    • AXON Clinical S.R.O
  • Zlín, Czechia, 76001
    • Gemini Eye Clinic
• France
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Bordeaux, France, 21 079
    • CHU Dijon
  • Créteil, France, 94010
    • Centre Hospitalier Intercommunal de Créteil
  • Paris, France, 75010
    • Hopital Lariboisiere
  • Paris, France, 75012
    • CHNO des Quinze-Vingts
  • Paris, France, 75015
    • Centre Ophtalmologique d'Imagerie et Laser
  • Strasbourg, France, 67091
    • CHU de Strasbourg Hopital Civil
  • Écully, France, 69130
    • Clinique du Val d'Ouest
• Germany
  • Bonn, Germany, 53127
    • Universitats-Augenklinik Bonn
  • Freiburg im Breisgau, Germany, 79106
    • University Opthalmology Clinic
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen Georg-August-Universität
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein
  • München, Germany, 80336
    • Augenklinik der LMU München
  • Münster, Germany, 48145
    • Augenzentrum am St. Franziskus-Hospital
  • Münster, Germany, 48149
    • Universitäts-Augenklinik
  • Tübingen, Germany, 72076
    • STZ Eyetrial
• Israel
  • Haifa, Israel, 3436212
    • Carmel Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Centre
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20157
    • Luigi Sacco Hospital
  • Roma, Italy, 128
    • IRCCS Fondazione G.B. Bietti
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Nijmegen, Netherlands, 6525
    • Radboud university medical center Oogheelkunde
• New Zealand
  • Christchurch, New Zealand, 8013
    • Southern Eye Specialists
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Eye Hospital
  • Bydgoszcz, Poland, 85-316
    • Oculomedica Eye Centre
  • Rzeszów, Poland, 35-017
    • Eye Surgery Center Professor Zagorski
• Spain
  • Barcelona, Spain, 08022
    • Centro Médico Teknon
  • Barcelona, Spain, 314
    • Centro de Oftalmologia Barraquer
  • Madrir
    • Majadahonda, Madrir, Spain, 2822
      • Hospital Universitario Puerta de Hierro
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • The Royal Victoria Hospital
  • Liverpool, United Kingdom, L7 8XP
    • Liverpool University Hospitals NHS Foundation Trust
  • Sunderland, United Kingdom, SR2 9HP
    • Sunderland Eye Infirmary
  • York, United Kingdom, YO31 8HE
    • York Teaching Hospital NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85021
      • Arizona Retina & Vitreous Consultants
  • California
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Campbell, California, United States, 95508
      • Retinal Diagnostic Center
    • Fullerton, California, United States, 92835
      • Retina Consultants of Orange County
    • Huntington Beach, California, United States, 92647
      • Atlantis Eyecare
    • La Jolla, California, United States, 92093
      • University of California, San Diego, Jacobs Retina
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Stanford, Stanford School of Medicine
    • Pasadena, California, United States, 91105
      • Doheny Eye Center UCLA
    • Poway, California, United States, 92064
      • Retina Consultants San Diego
    • Sacramento, California, United States, 95819
      • Retinal Consultants Med Group, Inc.
    • Santa Ana, California, United States, 92705
      • Orange County Retina Medical Group
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
  • Colorado
    • Durango, Colorado, United States, 81301
      • Southwest Retina Research Center, LLC
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England
  • Florida
    • Clearwater, Florida, United States, 33761
      • Blue Ocean Clinical Research / The Macula Center
    • Fort Myers, Florida, United States, 33912
      • National Ophthalmic Research Institute (Retina Consultants of Southwest Florida)
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
    • Naples, Florida, United States, 34103
      • Bascom Palmer Eye Institute of Naples
    • Pensacola, Florida, United States, 32503
      • Retina Specialty Institute
    • Winter Haven, Florida, United States, 33880
      • Center for Retina and Macular Disease
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, PC
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Gailey Eye Clinic Retina Center
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Feinberg School of Medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Retina and Vitreous Associates of Kentucky, PSC dba Retina Associates of Kentucky
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Retina Associates New Orleans
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • The Retina Care Center
    • Chevy Chase, Maryland, United States, 20815
      • The Retina Group of Washington
    • Hagerstown, Maryland, United States, 21740
      • Mid Atlantic Retina Specialists
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01107
      • New England Retina Consultants
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Medicine Kellogg Eye Center
    • Grand Rapids, Michigan, United States, 49564
      • Associated Retinal Consultants, P.C
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Vitreoretinal Surgery PA
  • Nevada
    • Reno, Nevada, United States, 89502
      • Sierra Eye Associates
  • New Jersey
    • Bloomfield, New Jersey, United States, 07003
      • Retina Center of NJ, LLC
    • Toms River, New Jersey, United States, 08755
      • NJ Retina
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Vision Research Center Eye Associates of NM
  • New York
    • Lynbrook, New York, United States, 11563
      • Ophthalmic Consultants of Long Island
    • New York, New York, United States, 10003
      • New York Eye and Ear Infirmary of Mount Sinai
    • New York, New York, United States, 10022
      • Vitreous Retina Macula Consultants of NY
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University, Duke Eye Center
  • Oklahoma
    • Edmond, Oklahoma, United States, 73013
      • Research - Retina Vitreous Center
  • Oregon
    • Eugene, Oregon, United States, 97405
      • Oregon Retina, LLP
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Mid Atlantic Retina
    • Monroeville, Pennsylvania, United States, 15146
      • Retina Vitreous Consultants
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina, Wills Eye Hospital
    • West Mifflin, Pennsylvania, United States, 15122
      • AIO Visionary Eye Care
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Charles Retina Institute
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina, PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Dallas, Texas, United States, 75231
      • Texas Retina Associates
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston, PA
    • Houston, Texas, United States, 77025
      • Houston Eye Associates
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • San Antonio, Texas, United States, 78240
      • Retinal Consultants of San Antonio
    • San Antonio, Texas, United States, 78240
      • Retina Associates of South Texas
    • San Antonio, Texas, United States, 78215
      • San Antonia Eye Center
    • San Antonio, Texas, United States, 78251
      • Brown Retina Institute
    • Willow Park, Texas, United States, 76087
      • Strategic Clinical Research Group
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah - John A. Moran Center
  • Virginia
    • Falls Church, Virginia, United States, 22046
      • Emerson Clinical Research Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: APL-2 15mg 0.1 mL Monthly for 24 months; A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every month	Drug: APL-2; Complement (C3) Inhibitor; Other Names: Pegcetacoplan
Experimental: APL-2 15mg 0.1 mL EOM for 24 months; A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month	Drug: APL-2; Complement (C3) Inhibitor; Other Names: Pegcetacoplan
Experimental: Sham Procedure Monthly for 24 months; Sham Procedure monthly for 24 months	Other: Sham Procedure; Subjects will receive a Sham procedure every month; Other: Sham Procedure; Subjects will receive a Sham procedure every other month
Experimental: Sham Procedure Every Other Month for 24 months; Sham Procedure every other month for 24 months	Other: Sham Procedure; Subjects will receive a Sham procedure every month; Other: Sham Procedure; Subjects will receive a Sham procedure every other month

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12	The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure (MMRM) model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24	The maximum reading speed of the study eye was calculated per Minnesota Low-Vision Reading Test (MNREAD) or Radner Reading Charts user manuals, with no adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute (wpm) was implemented. Maximum reading speed was calculated as the mean of the 3 highest non-zero reading speeds (or 2, or 1 value, as available), except when all wpm were calculated as 0 then the maximum reading speed was calculated as 0. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24	The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD subjects. It had 1 total index score. For each FRI Index reading activity performed in the past 7 days, subjects were asked about the extent to which they required assistance beyond eyeglasses/contact lenses, including the use of low-vision aids, adjustments in the activity, or help from another subject. Mean FRI Index scores ranged from 1 (unable to do independently) to 4 (totally independent), with higher scores indicating higher functional reading independence. A negative change from baseline indicated a decrease in the FRI; disease worsening. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24	The NL-BCVA was assessed by early treatment diabetic retinopathy study (ETDRS) chart prior to dilating the eyes at a starting distance of 4 meters and ranged from 0 (least score) to 100 (best score). If the 4-meter score was >19 letters read correctly, the visual acuity score was the sum of total letters correctly read at 4 meters plus the addition of 30. If the 4-meter score was ≤19 letters read correctly, the visual acuity score was the sum of total letters read correctly at 4 meters and total letters read correctly at the 1-meter distance. If no letters were read correctly at either the 4-meter distance or the 1-meter distance, the visual acuity score was 0. A positive change in the value indicated improvement in visual acuity. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
LS Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 24	The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a mixed effect model for repeated measure model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24	The mean change in GA lesion area through Month 24 was measured by assuming a piecewise linear trend in time with knots by FAF images at Months 6, 12, 18, and 24 and was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	From Baseline (screening) through Month 24
LS Mean Change From Baseline in Mean Threshold Sensitivity of All Points of the Study Eye at Month 24	Mean threshold sensitivity of all points was determined from the mesopic microperimetry as an assessment of the macular functional response. Microperimetry offers the option to test retinal light sensitivity while directly observing the fundus and allows for monitoring of macular function loss associated with GA progression. The microperimetry reading center overlaid the baseline FAF images with GA lesions traced by the imaging reading center and the corresponding macular integrity assessment microperimetry baseline scanning laser ophthalmoscope image and identified perilesional (within 500 microns outside the atrophy border), paralesional (beyond 500 microns outside the atrophy border), and extralesional (outside the atrophy border) loci on the microperimetry grid to determine the mean threshold sensitivity for these 3 areas. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2018
• Primary Completion (Actual): June 28, 2021
• Study Completion (Actual): June 28, 2022

Study Registration Dates

• First Submitted: April 20, 2018
• First Submitted That Met QC Criteria: May 3, 2018
• First Posted (Actual): May 15, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: June 29, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Pathological Conditions, Anatomical; Macular Degeneration; Geographic Atrophy; Atrophy
• Other Study ID Numbers: APL2-304

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No