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

NCT ID: NCT03525600

Last Updated: 2023-06-18

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

621 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-08-31

Study Completion Date

2022-06-20

Brief Summary

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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.

Detailed Description

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Conditions

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Geographic Atrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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

Group Type EXPERIMENTAL

APL-2

Intervention Type DRUG

Complement (C3) Inhibitor

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

Group Type EXPERIMENTAL

APL-2

Intervention Type DRUG

Complement (C3) Inhibitor

Sham Procedure Monthly for 24 months

Sham Procedure for 24 months

Group Type EXPERIMENTAL

Sham Procedure

Intervention Type OTHER

Subjects will receive a Sham procedure every month

Sham Procedure Every Other Month for 24 months

Sham Procedure every other month for 24 months

Group Type EXPERIMENTAL

Sham Procedure

Intervention Type OTHER

Subjects will receive a Sham procedure every other month

Interventions

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APL-2

Complement (C3) Inhibitor

Intervention Type DRUG

APL-2

Complement (C3) Inhibitor

Intervention Type DRUG

Sham Procedure

Subjects will receive a Sham procedure every month

Intervention Type OTHER

Sham Procedure

Subjects will receive a Sham procedure every other month

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* 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

* 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.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Apellis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Retinal Research Institute

Phoenix, Arizona, United States

Site Status

Associated Retina Consultants, Ltd

Phoenix, Arizona, United States

Site Status

Retina Institute of California dba Acuity Eye Grp

Arcadia, California, United States

Site Status

California Retina Consultants

Bakersfield, California, United States

Site Status

Retina Vitreous Associates Medical Group

Beverly Hills, California, United States

Site Status

The Retina Partners

Encino, California, United States

Site Status

The Gavin Herbert Eye Institute/UC Irvine

Irvine, California, United States

Site Status

Northern California Retina Vitreous Associates

Mountain View, California, United States

Site Status

Retina Institute of California Medical Group

Palm Desert, California, United States

Site Status

Byers Eye Institute at Standford, Stanford School of Medicine

Palo Alto, California, United States

Site Status

Retina Consultants San Diego

Poway, California, United States

Site Status

Retina Consultants of Southern California

Redlands, California, United States

Site Status

California Retina Consultants

Santa Barbara, California, United States

Site Status

Bay Area Retina Associates

Walnut Creek, California, United States

Site Status

Danbury Eye Physicians & Surgeons, P.C. - Danbury

Danbury, Connecticut, United States

Site Status

New England Retina Associates

Hamden, Connecticut, United States

Site Status

Retina Group of New England,PC

Waterford, Connecticut, United States

Site Status

Florida Eye Microsurgical Institute, Inc.

Boynton Beach, Florida, United States

Site Status

Pinnacle Research Institute

Fort Lauderdale, Florida, United States

Site Status

Retina Health Center

Fort Myers, Florida, United States

Site Status

Bascom Palmer Eye Institute

Palm Beach Gardens, Florida, United States

Site Status

Eye Associates of Pinellas

Pinellas Park, Florida, United States

Site Status

East Florida Eye Institute

Stuart, Florida, United States

Site Status

Southern Vitreoretinal Associates

Tallahassee, Florida, United States

Site Status

Retina Associates of Florida

Tampa, Florida, United States

Site Status

University of South Florida (USF) Eye Institute

Tampa, Florida, United States

Site Status

Southeast Retina Center, PC

Augusta, Georgia, United States

Site Status

Georgia Retina

Marietta, Georgia, United States

Site Status

Midwest Eye Institute

Indianapolis, Indiana, United States

Site Status

Sabates Eye Center

Leawood, Kansas, United States

Site Status

Elman Retina Group, PA

Baltimore, Maryland, United States

Site Status

Cumberland Valley Retina Consultants, PC

Hagerstown, Maryland, United States

Site Status

Mid Atlantic Retina Specialists

Hagerstown, Maryland, United States

Site Status

Retina Specialists

Towson, Maryland, United States

Site Status

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Site Status

New England Retina Consultants, PC

Springfield, Massachusetts, United States

Site Status

Associated Retinal Consultants, P.C

Grand Rapids, Michigan, United States

Site Status

Retina Specialists of Michigan / Foundation for Vision

Grand Rapids, Michigan, United States

Site Status

Retina Consultants of Michigan

Southfield, Michigan, United States

Site Status

Associated Retinal Consultants PC

Traverse City, Michigan, United States

Site Status

Sierra Eye Associates

Reno, Nevada, United States

Site Status

Retina Associates of New Jersey (NJ Retina)

Teaneck, New Jersey, United States

Site Status

Long Island Vitreoretinal Consultants

Great Neck, New York, United States

Site Status

Vitreous Retina Macula Consultants of NY

New York, New York, United States

Site Status

Western Carolina Retinal Associates

Asheville, North Carolina, United States

Site Status

Charlotte Eye Ear Nose and Throat Associates, PS

Charlotte, North Carolina, United States

Site Status

Graystone Eye

Hickory, North Carolina, United States

Site Status

Retina Associates of Cleveland, Inc.

Cleveland, Ohio, United States

Site Status

Retina Associates of Cleveland, Inc

Cleveland, Ohio, United States

Site Status

Retina Associates of Cleveland

Cleveland, Ohio, United States

Site Status

Cleveland Clinic, Cole Eye Institute

Cleveland, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Retina Associates of Cleveland, Inc.

Youngstown, Ohio, United States

Site Status

Retina Northwest, PC

Portland, Oregon, United States

Site Status

Eye Health Northwest

Portland, Oregon, United States

Site Status

Mid Atlantic Retina

Philadelphia, Pennsylvania, United States

Site Status

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States

Site Status

Tennessee Retina, PC

Nashville, Tennessee, United States

Site Status

Retina Research Institute of Texas

Abilene, Texas, United States

Site Status

Southwest Retina Specialists

Amarillo, Texas, United States

Site Status

Retina Consultants of Austin (Retina Research Center)

Austin, Texas, United States

Site Status

Retina Consultants of Houston, PA

Houston, Texas, United States

Site Status

Valley Retina Institute, PA

McAllen, Texas, United States

Site Status

Medical Center Ophthalmology Associates

San Antonio, Texas, United States

Site Status

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Site Status

Retina Consultants of Houston

The Woodlands, Texas, United States

Site Status

Retina Associates of Utah, PC

Murray, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

The Retina Group of Washington

Fairfax, Virginia, United States

Site Status

Virginia Retina Center

Warrenton, Virginia, United States

Site Status

Vitreoretinal Associates of Washington

Bellevue, Washington, United States

Site Status

Spokane Eye Clinical Research

Spokane, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Fundacion Zambrano

Buenos Aires, Buenos Aires F.D., Argentina

Site Status

Microcirugia Ocular

El Rosario, Corrientes Province, Argentina

Site Status

Grupo Laser Vision

Rosario, Santa Fe Province, Argentina

Site Status

Organizacion Medica de investigacion

Buenos Aires, , Argentina

Site Status

Centro Oftalmologico Dr Charles

Buenos Aires, , Argentina

Site Status

Diagnostico Ocular

Buenos Aires, , Argentina

Site Status

Centro Privado de Ojos Romagosa SA

Córdoba, , Argentina

Site Status

Instituto Oftalmologico de Cordoba

Córdoba, , Argentina

Site Status

Oftar Mendoza SRL

Mendoza, , Argentina

Site Status

Oftalmologos Especialistas

Rosario, , Argentina

Site Status

Sydney Retina

Sydney, New South Wales, Australia

Site Status

Centre for Eye Research Australia

East Melbourne, Victoria, Australia

Site Status

Retina and Eye Consultants

Hurstville, , Australia

Site Status

Clinica Ocular Oftalmologia LTDA

Vitória, Espírito Santo, Brazil

Site Status

Clinica Oftalmologica Sao Lucas

Osasco, São Paulo, Brazil

Site Status

IPEPO - Instituto Da Visao

São Paulo, Vila Clementino, Brazil

Site Status

Instituto da Visão - Hospital de Olhos Ltda

Belo Horizonte, , Brazil

Site Status

Hospital De Clinicas De Porto Alegre

Porto Alegre, , Brazil

Site Status

UNIFESP - Federal University

São Paulo, , Brazil

Site Status

Ivey Eye Institute

London, Ontario, Canada

Site Status

University of Ottawa Eye Institute

Ottawa, Ontario, Canada

Site Status

DRY AMD Clinic - St. Michael's Hospital

Toronto, Ontario, Canada

Site Status

Retina Centre of Ottawa

Ottawa, , Canada

Site Status

Fakultní nemocnice Ostrava

Ostrava-Poruba, , Czechia

Site Status

OFTEX Eye Clinic

Pardubice, , Czechia

Site Status

AXON Clinical, S.R.O.

Prague, , Czechia

Site Status

University Hospital Kralovske Vinochrady

Vinohrady, , Czechia

Site Status

Centre Hospitalier Intercommunal de Créteil

Créteil, , France

Site Status

Hopital de la Croix-Rousse

Lyon, , France

Site Status

Centre Monticelli Paradis

Marseille, , France

Site Status

CHU de Nantes - Hotel Dieu

Nantes, , France

Site Status

Centre Ophtalmologique de l´Odéon

Paris, , France

Site Status

Centre Ophthalmologique Saint-Exupery

Saint-Cyr-sur-Loire, , France

Site Status

Maison Rouge Ophthalmologic Center

Strasbourg, , France

Site Status

Universitäts-Augenklinik Bonn

Bonn, , Germany

Site Status

University Hospital Cologne

Cologne, , Germany

Site Status

Klinikum der Stadt Ludwigshafen gGmbH

Ludwigshafen, , Germany

Site Status

Klinikum rechts der Isar

München, , Germany

Site Status

Universitätsklinikum Regensburg

Regensburg, , Germany

Site Status

University Hospital Würzburg

Würzburg, , Germany

Site Status

Shamir Medical Center

Be’er Ya‘aqov, , Israel

Site Status

Rambam Medical Center

Haifa, , Israel

Site Status

Meir Medical Center

Kfar Saba, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Ospedale San Raffaele

Milan, , Italy

Site Status

Luigi Sacco Hospital

Milan, , Italy

Site Status

Retina Specialist

Auckland, , New Zealand

Site Status

Hamilton Eye Clinic

Hamilton, , New Zealand

Site Status

Oftalmika Eye Hospital

Bydgoszcz, , Poland

Site Status

Jasne Blonia Eye Clinic

Lodz, , Poland

Site Status

Centrum Diagnostyki i Mikrochirurgii Oka - LENS

Olsztyn, , Poland

Site Status

Centrum Medyczne UNO-MED

Tarnów, , Poland

Site Status

Emanuelli Research and Development Center

Arecibo, , Puerto Rico

Site Status

Centro Médico Teknon

Barcelona, , Spain

Site Status

Instituto Oftalmologico Gómez-Ulla

Santiago de Compostela, , Spain

Site Status

Hospital Universitario Rio Hortega

Valladolid, , Spain

Site Status

Moorfields Eye Hospital NHS Foundation Trust

London, England, United Kingdom

Site Status

Eye Clinic, Acre Mill Outpatients, Huddersfield Royal Infirmary

Huddersfield, West Yorkshire, United Kingdom

Site Status

Bristol Eye Hospital

Bristol, , United Kingdom

Site Status

St James's University Hospital

Leeds, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

London North West University Hospital Trust

London, , United Kingdom

Site Status

King's College Hospital NHS Trust

London, , United Kingdom

Site Status

Oxford Eye Hospital

Oxford, , United Kingdom

Site Status

Salisbury NHS Foundation Trust

Salisbury, , United Kingdom

Site Status

Sunderland Eye Infirmary

Sunderland, , United Kingdom

Site Status

Countries

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United States Argentina Australia Brazil Canada Czechia France Germany Israel Italy New Zealand Poland Puerto Rico Spain United Kingdom

References

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Sadda S, Hatcher KA, Shah BK, Kondapalli SS, Li C, Baumal CR. Outer Retinal Tubulation and Geographic Atrophy: A Natural History Analysis of Sham Observed Eyes from the OAKS and DERBY Trials. Ophthalmol Ther. 2025 Jul;14(7):1611-1619. doi: 10.1007/s40123-025-01156-5. Epub 2025 May 19.

Reference Type DERIVED
PMID: 40388106 (View on PubMed)

Wykoff CC, Holz FG, Chiang A, Boyer D, Dhoot DS, Loewenstein A, Mones J, Heier J, Abbey AM, Singerman LJ, Vajzovic L, Lin J, Li C, Vilupuru A, Baumal CR; OAKS, DERBY, and GALE Investigators. Pegcetacoplan Treatment for Geographic Atrophy in Age-Related Macular Degeneration Over 36 Months: Data From OAKS, DERBY, and GALE. Am J Ophthalmol. 2025 Aug;276:350-364. doi: 10.1016/j.ajo.2025.04.016. Epub 2025 Apr 23.

Reference Type DERIVED
PMID: 40280279 (View on PubMed)

Fu DJ, Bagga P, Naik G, Glinton S, Faes L, Liefers B, Lima R, Wignall G, Keane PA, Ioannidou E, Ribeiro Reis AP, McKeown A, Scheibler L, Patel PJ, Moghul I, Pontikos N, Balaskas K. Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months. JAMA Ophthalmol. 2024 Jun 1;142(6):548-558. doi: 10.1001/jamaophthalmol.2024.1269.

Reference Type DERIVED
PMID: 38722644 (View on PubMed)

Heier JS, Lad EM, Holz FG, Rosenfeld PJ, Guymer RH, Boyer D, Grossi F, Baumal CR, Korobelnik JF, Slakter JS, Waheed NK, Metlapally R, Pearce I, Steinle N, Francone AA, Hu A, Lally DR, Deschatelets P, Francois C, Bliss C, Staurenghi G, Mones J, Singh RP, Ribeiro R, Wykoff CC; OAKS and DERBY study investigators. Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials. Lancet. 2023 Oct 21;402(10411):1434-1448. doi: 10.1016/S0140-6736(23)01520-9.

Reference Type DERIVED
PMID: 37865470 (View on PubMed)

Tzoumas N, Riding G, Williams MA, Steel DH. Complement inhibitors for age-related macular degeneration. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD009300. doi: 10.1002/14651858.CD009300.pub3.

Reference Type DERIVED
PMID: 37314061 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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APL2-303

Identifier Type: -

Identifier Source: org_study_id

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