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): 621
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1015 ABO
    • Organizacion Medica de Investigacion
  • Buenos Aires, Argentina, C1116ABA
    • Centro Oftalmologico Dr Charles
  • Buenos Aires, Argentina, C1425BGE
    • Diagnostico Ocular
  • Córdoba, Argentina, X5000III
    • Instituto Oftalmológico de Córdoba
  • Córdoba, Argentina, X5000AAJ
    • Centro Privado de Ojos Romagosa SA
  • Mendoza, Argentina, 5500
    • Oftar Mendoza SRL
  • Rosario, Argentina, 1288
    • Oftalmólogos Especialistas
  • Capital Federal
    • Buenos Aires, Capital Federal, Argentina, C1023 AAQ
      • Fundacion Zambrano
  • Corrientes
    • Rosario, Corrientes, Argentina, 2000
      • Microcirugia Ocular
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000 AZH
      • Grupo Laser Vision
• Australia
  • Hurstville, Australia, NSW 2220
    • Retina and Eye Consultants
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Sydney Retina
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Centre for Eye Research Australia
• Brazil
  • Belo Horizonte, Brazil, 32150-274
    • Instituto da Visão - Hospital de Olhos Ltda
  • Porto Alegre, Brazil, 90036-903
    • Hospital de Clinicas de Porto Alegre
  • São Paulo, Brazil, 04021-001
    • UNIFESP - Federal University
  • Espirito Santo
    • Vitória, Espirito Santo, Brazil, 29055-45
      • Clinica Ocular Oftalmologia LTDA
  • Sao Paulo
    • Osasco, Sao Paulo, Brazil, 06010-130
      • Clinica Oftalmologica Sao Lucas
  • Vila Clementino
    • São Paulo, Vila Clementino, Brazil, 04038-032
      • IPEPO - Instituto da Visao
• Canada
  • Ottawa, Canada, K2B 7E9
    • Retina Centre of Ottawa
  • Ontario
    • London, Ontario, Canada, N6A
      • Ivey Eye Institute
    • Ottawa, Ontario, Canada, K1H 8L6
      • University of Ottawa Eye Institute
    • Toronto, Ontario, Canada, M5C 1R6
      • DRY AMD Clinic - St. Michael's Hospital
• Czechia
  • Ostrava-Poruba, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Pardubice, Czechia, 53002
    • OFTEX Eye Clinic
  • Praha, Czechia, 150 00
    • Axon Clinical, s.r.o.
  • Vinohrady, Czechia, 100 34
    • University Hospital Kralovske Vinochrady
• France
  • Créteil, France
    • Centre Hospitalier Intercommunal de Creteil
  • Lyon, France, 69004
    • Hôpital de la Croix-Rousse
  • Marseille, France, 13008
    • Centre monticelli Paradis
  • Nantes, France, 44093
    • CHU de Nantes - Hôtel Dieu
  • Paris, France, 75006
    • Centre Ophtalmologique de l´Odéon
  • Saint-Cyr-sur-Loire, France, 37540
    • Centre Ophthalmologique Saint-Exupery
  • Strasbourg, France, 67000
    • Maison Rouge Ophthalmologic Center
• Germany
  • Bonn, Germany, 53127
    • Universitats-Augenklinik Bonn
  • Cologne, Germany, 50937
    • University Hospital Cologne
  • Ludwigshafen, Germany, 67063
    • Klinikum der Stadt Ludwigshafen gGmbH
  • München, Germany, 81675
    • Klinikum rechts der Isar
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Würzburg, Germany, 97080
    • University Hospital Würzburg
• Israel
  • Be'er Ya'aqov, Israel, 7030000
    • Shamir Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Petah tikva, Israel, 49100
    • Rabin Medical Center
  • Reẖovot, Israel, 76100
    • Kaplan Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Milano, Italy, 20132
    • Ospedale San Raffaele
  • Milano, Italy, 20157
    • Luigi Sacco Hospital
• New Zealand
  • Auckland, New Zealand, 1052
    • Retina Specialist
  • Hamilton, New Zealand, 3204
    • Hamilton Eye Clinic
• Poland
  • Bydgoszcz, Poland, 85-631
    • Oftalmika Eye Hospital
  • Olsztyn, Poland, 10-424
    • Centrum Diagnostyki i Mikrochirurgii Oka - LENS
  • Tarnow, Poland, 33-100
    • Centrum Medyczne UNO-MED
  • Łódź, Poland, 91-134
    • Jasne Blonia Eye Clinic
• Puerto Rico
  • Arecibo, Puerto Rico, 00612
    • Emanuelli Research and Development Center
• Spain
  • Barcelona, Spain, 08022
    • Centro Médico Teknon
  • Santiago De Compostela, Spain, 15706
    • Instituto Oftalmológico Gómez-Ulla
  • Valladolid, Spain, 47006
    • Hospital Universitario Río Hortega
• United Kingdom
  • Bristol, United Kingdom, BS1 2LX
    • Bristol Eye Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital
  • Leicester, United Kingdom, LEI 5WW
    • Leicester Royal Infirmary
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Trust
  • London, United Kingdom, NW10 7NS
    • London North West University Hospital Trust
  • Oxford, United Kingdom, OX3 9DU
    • Oxford Eye Hospital
  • Salisbury, United Kingdom, SP2 8BJ
    • Salisbury NHS Foundation Trust
  • Sunderland, United Kingdom, SR2 9HP
    • Sunderland Eye Infirmary
  • England
    • London, England, United Kingdom, EC1V 2PD
      • Moorfields Eye Hospital NHS Foundation Trust
  • West Yorkshire
    • Huddersfield, West Yorkshire, United Kingdom, HD3 3EA
      • Eye Clinic, Acre Mill Outpatients, Huddersfield Royal Infirmary
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85014
      • Retinal Research Institute
    • Phoenix, Arizona, United States, 85020
      • Associated Retina Consultants, Ltd
  • California
    • Arcadia, California, United States, 91007
      • Retina Institute of California dba Acuity Eye Grp
    • Bakersfield, California, United States, 93309
      • California Retina Consultants
    • Beverly Hills, California, United States, 90211
      • Retina Vitreous Associates Medical Group
    • Encino, California, United States, 91436
      • The Retina Partners
    • Irvine, California, United States, 92697
      • The Gavin Herbert Eye Institute/UC Irvine
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Palm Desert, California, United States, 92260
      • Retina Institute of California Medical Group
    • Palo Alto, California, United States, 94303
      • Byers Eye Institute at Standford, Stanford School of Medicine
    • Poway, California, United States, 92064
      • Retina Consultants San Diego
    • Redlands, California, United States, 92374
      • Retina Consultants of Southern California
    • Santa Barbara, California, United States, 93103
      • California Retina Consultants
    • Walnut Creek, California, United States, 94598
      • Bay Area Retina Associates
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Danbury Eye Physicians & Surgeons, P.C. - Danbury
    • Hamden, Connecticut, United States, 06518
      • New England Retina Associates
    • Waterford, Connecticut, United States, 06385
      • Retina Group of New England,PC
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Institute, Inc.
    • Fort Lauderdale, Florida, United States, 33309
      • Pinnacle Research Institute
    • Fort Myers, Florida, United States, 33907
      • Retina Health Center
    • Palm Beach Gardens, Florida, United States, 33418
      • Bascom Palmer Eye Institute
    • Pinellas Park, Florida, United States, 33782
      • Eye Associates of Pinellas
    • Stuart, Florida, United States, 34994
      • East Florida Eye Institute
    • Tallahassee, Florida, United States, 32308
      • Southern Vitreoretinal Associates
    • Tampa, Florida, United States, 33609
      • Retina Associates of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida (USF) Eye Institute
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeast Retina Center, PC
    • Marietta, Georgia, United States, 30060
      • Georgia Retina
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Sabates Eye Center
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Elman Retina Group, PA
    • Hagerstown, Maryland, United States, 21740
      • Mid Atlantic Retina Specialists
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants, PC
    • Towson, Maryland, United States, 21204
      • Retina Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
    • Springfield, Massachusetts, United States, 01107
      • New England Retina Consultants, PC
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Associated Retinal Consultants, P.C
    • Grand Rapids, Michigan, United States, 49546
      • Retina Specialists of Michigan / Foundation for Vision
    • Southfield, Michigan, United States, 48034
      • Retina Consultants of Michigan
    • Traverse City, Michigan, United States, 49686
      • Associated Retinal Consultants PC
  • Nevada
    • Reno, Nevada, United States, 89503
      • Sierra Eye Associates
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Retina Associates of New Jersey (NJ Retina)
  • New York
    • Great Neck, New York, United States, 11021
      • Long Island Vitreoretinal Consultants
    • New York, New York, United States, 10022
      • Vitreous Retina Macula Consultants of NY
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Western Carolina Retinal Associates
    • Charlotte, North Carolina, United States, 28210
      • Charlotte Eye Ear Nose and Throat Associates, PS
    • Hickory, North Carolina, United States, 28602
      • Graystone Eye
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Retina Associates of Cleveland, Inc.
    • Cleveland, Ohio, United States, 44130
      • Retina Associates of Cleveland
    • Cleveland, Ohio, United States, 44122
      • Retina Associates of Cleveland, INC
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, Cole Eye Institute
    • Columbus, Ohio, United States, 43212
      • The Ohio State University
    • Youngstown, Ohio, United States, 44505
      • Retina Associates of Cleveland, Inc.
  • Oregon
    • Portland, Oregon, United States, 97221
      • Retina Northwest, PC
    • Portland, Oregon, United States, 97225
      • Eye Health Northwest
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19006
      • Mid Atlantic Retina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Retina, PC
  • Texas
    • Abilene, Texas, United States, 79606
      • Retina Research Institute of Texas
    • Amarillo, Texas, United States, 79106
      • Southwest Retina Specialists
    • Austin, Texas, United States, 78705
      • Retina Consultants of Austin (Retina Research Center)
    • Houston, Texas, United States, 77030
      • Retina Consultants of Houston, PA
    • McAllen, Texas, United States, 78503
      • Valley Retina Institute, PA
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
    • San Antonio, Texas, United States, 78240
      • Retinal Consultants of San Antonio
    • The Woodlands, Texas, United States, 77384
      • Retina Consultants of Houston
  • Utah
    • Murray, Utah, United States, 84107
      • Retina Associates of Utah, PC
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • The Retina Group of Washington
    • Warrenton, Virginia, United States, 20186
      • Virginia Retina Center
  • Washington
    • Bellevue, Washington, United States, 98004
      • Vitreoretinal Associates of Washington
    • Spokane, Washington, United States, 99204
      • Spokane Eye Clinical Research
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • 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.

• Female subjects must be:

  • Women of non-child-bearing potential (WONCBP), or
  • Women of child-bearing potential (WOCBP) with a negative serum 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.
• 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 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
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
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
Experimental: Sham Procedure Monthly for 24 months; Sham Procedure 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 the 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 MMRM 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, and 18 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 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

Collaborators and Investigators

• Sponsor: Apellis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2018
• Primary Completion (Actual): June 21, 2021
• Study Completion (Actual): June 20, 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 (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 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: APL2-303

Drug and device information, study documents

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