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

NCT03525600 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: APL2-303
• Study Type: interventional
• Target: 621
• Locations: 15 countries
• Sites: 141

Brief 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.

Conditions

Geographic Atrophy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• LS Mean Change From Baseline in the Total Area of GA Lesions in the Study Eye at Month 24

  Baseline (screening) and Month 24

• Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24

  From Baseline (screening) through Month 24

• LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24

  Baseline (screening) and Month 24

• LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24

  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

  Baseline (screening) and Month 24

Study Arms (4)

APL-2 15mg 0.1 mL monthly for 24 months

EXPERIMENTAL

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

APL-2 15mg 0.1 mL EOM for 24 months

EXPERIMENTAL

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

Sham Procedure Monthly for 24 months

EXPERIMENTAL

Sham Procedure for 24 months

Other: Sham Procedure

Sham Procedure Every Other Month for 24 months

EXPERIMENTAL

Sham Procedure every other month for 24 months

Other: Sham Procedure

Interventions

APL-2 DRUG

Complement (C3) Inhibitor

APL-2 15mg 0.1 mL monthly for 24 months

Sham Procedure OTHER

Subjects will receive a Sham procedure every month

Sham Procedure Monthly for 24 months

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
• History of laser therapy in the macular region.
• 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.
• 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.

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (141)

Retinal Research Institute

Phoenix, Arizona, 85014, United States

Location

Associated Retina Consultants, Ltd

Phoenix, Arizona, 85020, United States

Location

Retina Institute of California dba Acuity Eye Grp

Arcadia, California, 91007, United States

Location

California Retina Consultants

Bakersfield, California, 93309, United States

Location

Retina Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

The Retina Partners

Encino, California, 91436, United States

Location

The Gavin Herbert Eye Institute/UC Irvine

Irvine, California, 92697, United States

Location

Northern California Retina Vitreous Associates

Mountain View, California, 94040, United States

Location

Retina Institute of California Medical Group

Palm Desert, California, 92260, United States

Location

Byers Eye Institute at Standford, Stanford School of Medicine

Palo Alto, California, 94303, United States

Location

Retina Consultants San Diego

Poway, California, 92064, United States

Location

Retina Consultants of Southern California

Redlands, California, 92374, United States

Location

California Retina Consultants

Santa Barbara, California, 93103, United States

Location

Bay Area Retina Associates

Walnut Creek, California, 94598, United States

Location

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

Danbury, Connecticut, 06810, United States

Location

New England Retina Associates

Hamden, Connecticut, 06518, United States

Location

Retina Group of New England,PC

Waterford, Connecticut, 06385, United States

Location

Florida Eye Microsurgical Institute, Inc.

Boynton Beach, Florida, 33426, United States

Location

Pinnacle Research Institute

Fort Lauderdale, Florida, 33309, United States

Location

Retina Health Center

Fort Myers, Florida, 33907, United States

Location

Bascom Palmer Eye Institute

Palm Beach Gardens, Florida, 33418, United States

Location

Eye Associates of Pinellas

Pinellas Park, Florida, 33782, United States

Location

East Florida Eye Institute

Stuart, Florida, 34994, United States

Location

Southern Vitreoretinal Associates

Tallahassee, Florida, 32308, United States

Location

Retina Associates of Florida

Tampa, Florida, 33609, United States

Location

University of South Florida (USF) Eye Institute

Tampa, Florida, 33612, United States

Location

Southeast Retina Center, PC

Augusta, Georgia, 30909, United States

Location

Georgia Retina

Marietta, Georgia, 30060, United States

Location

Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

Location

Sabates Eye Center

Leawood, Kansas, 66211, United States

Location

Elman Retina Group, PA

Baltimore, Maryland, 21236, United States

Location

Cumberland Valley Retina Consultants, PC

Hagerstown, Maryland, 21740, United States

Location

Mid Atlantic Retina Specialists

Hagerstown, Maryland, 21740, United States

Location

Retina Specialists

Towson, Maryland, 21204, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

New England Retina Consultants, PC

Springfield, Massachusetts, 01107, United States

Location

Associated Retinal Consultants, P.C

Grand Rapids, Michigan, 49546, United States

Location

Retina Specialists of Michigan / Foundation for Vision

Grand Rapids, Michigan, 49546, United States

Location

Retina Consultants of Michigan

Southfield, Michigan, 48034, United States

Location

Associated Retinal Consultants PC

Traverse City, Michigan, 49686, United States

Location

Sierra Eye Associates

Reno, Nevada, 89503, United States

Location

Retina Associates of New Jersey (NJ Retina)

Teaneck, New Jersey, 07666, United States

Location

Long Island Vitreoretinal Consultants

Great Neck, New York, 11021, United States

Location

Vitreous Retina Macula Consultants of NY

New York, New York, 10022, United States

Location

Western Carolina Retinal Associates

Asheville, North Carolina, 28803, United States

Location

Charlotte Eye Ear Nose and Throat Associates, PS

Charlotte, North Carolina, 28210, United States

Location

Graystone Eye

Hickory, North Carolina, 28602, United States

Location

Retina Associates of Cleveland, Inc.

Cleveland, Ohio, 44122, United States

Location

Retina Associates of Cleveland, Inc

Cleveland, Ohio, 44122, United States

Location

Retina Associates of Cleveland

Cleveland, Ohio, 44130, United States

Location

Cleveland Clinic, Cole Eye Institute

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43212, United States

Location

Retina Associates of Cleveland, Inc.

Youngstown, Ohio, 44505, United States

Location

Retina Northwest, PC

Portland, Oregon, 97221, United States

Location

Eye Health Northwest

Portland, Oregon, 97225, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19006, United States

Location

Black Hills Regional Eye Institute

Rapid City, South Dakota, 57701, United States

Location

Tennessee Retina, PC

Nashville, Tennessee, 37203, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Southwest Retina Specialists

Amarillo, Texas, 79106, United States

Location

Retina Consultants of Austin (Retina Research Center)

Austin, Texas, 78705, United States

Location

Retina Consultants of Houston, PA

Houston, Texas, 77030, United States

Location

Valley Retina Institute, PA

McAllen, Texas, 78503, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Retina Consultants of Houston

The Woodlands, Texas, 77384, United States

Location

Retina Associates of Utah, PC

Murray, Utah, 84107, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

The Retina Group of Washington

Fairfax, Virginia, 22031, United States

Location

Virginia Retina Center

Warrenton, Virginia, 20186, United States

Location

Vitreoretinal Associates of Washington

Bellevue, Washington, 98004, United States

Location

Spokane Eye Clinical Research

Spokane, Washington, 99204, United States

Location

University of Wisconsin

Madison, Wisconsin, 53715, United States

Location

Fundacion Zambrano

Buenos Aires, Buenos Aires F.D., C1023 AAQ, Argentina

Location

Microcirugia Ocular

El Rosario, Corrientes Province, 2000, Argentina

Location

Grupo Laser Vision

Rosario, Santa Fe Province, S2000 AZH, Argentina

Location

Organizacion Medica de investigacion

Buenos Aires, C1015 ABO, Argentina

Location

Centro Oftalmologico Dr Charles

Buenos Aires, C1116ABA, Argentina

Location

Diagnostico Ocular

Buenos Aires, C1425BGE, Argentina

Location

Centro Privado de Ojos Romagosa SA

Córdoba, X5000AAJ, Argentina

Location

Instituto Oftalmologico de Cordoba

Córdoba, X5000III, Argentina

Location

Oftar Mendoza SRL

Mendoza, 5500, Argentina

Location

Oftalmologos Especialistas

Rosario, 1288, Argentina

Location

Sydney Retina

Sydney, New South Wales, 2000, Australia

Location

Centre for Eye Research Australia

East Melbourne, Victoria, 3002, Australia

Location

Retina and Eye Consultants

Hurstville, NSW 2220, Australia

Location

Clinica Ocular Oftalmologia LTDA

Vitória, Espírito Santo, 29055-45, Brazil

Location

Clinica Oftalmologica Sao Lucas

Osasco, São Paulo, 06010-130, Brazil

Location

IPEPO - Instituto Da Visao

São Paulo, Vila Clementino, 04038-032, Brazil

Location

Instituto da Visão - Hospital de Olhos Ltda

Belo Horizonte, 32150-274, Brazil

Location

Hospital De Clinicas De Porto Alegre

Porto Alegre, 90036-903, Brazil

Location

UNIFESP - Federal University

São Paulo, 04021-001, Brazil

Location

Ivey Eye Institute

London, Ontario, N6A, Canada

Location

University of Ottawa Eye Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

DRY AMD Clinic - St. Michael's Hospital

Toronto, Ontario, M5C 1R6, Canada

Location

Retina Centre of Ottawa

Ottawa, K2B 7E9, Canada

Location

University Hospital Kralovske Vinochrady

Brno-Vinohrady, 100 34, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

OFTEX Eye Clinic

Pardubice, 53002, Czechia

Location

AXON Clinical, S.R.O.

Prague, 150 00, Czechia

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Location

Hopital de la Croix-Rousse

Lyon, 69004, France

Location

Centre Monticelli Paradis

Marseille, 13008, France

Location

CHU de Nantes - Hotel Dieu

Nantes, 44093, France

Location

Centre Ophtalmologique de l´Odéon

Paris, 75006, France

Location

Centre Ophthalmologique Saint-Exupery

Saint-Cyr-sur-Loire, 37540, France

Location

Maison Rouge Ophthalmologic Center

Strasbourg, 67000, France

Location

Universitäts-Augenklinik Bonn

Bonn, 53127, Germany

Location

University Hospital Cologne

Cologne, 50937, Germany

Location

Klinikum der Stadt Ludwigshafen gGmbH

Ludwigshafen, 67063, Germany

Location

Klinikum rechts der Isar

München, 81675, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

University Hospital Würzburg

Würzburg, 97080, Germany

Location

Shamir Medical Center

Be’er Ya‘aqov, 7030000, Israel

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Meir Medical Center

Kfar Saba, 4428164, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Luigi Sacco Hospital

Milan, 20157, Italy

Location

Retina Specialist

Auckland, 1052, New Zealand

Location

Hamilton Eye Clinic

Hamilton, 3204, New Zealand

Location

Oftalmika Eye Hospital

Bydgoszcz, 85-631, Poland

Location

Jasne Blonia Eye Clinic

Lodz, 91-134, Poland

Location

Centrum Diagnostyki i Mikrochirurgii Oka - LENS

Olsztyn, 10-424, Poland

Location

Centrum Medyczne UNO-MED

Tarnów, 33-100, Poland

Location

Emanuelli Research and Development Center

Arecibo, 00612, Puerto Rico

Location

Centro Médico Teknon

Barcelona, 08022, Spain

Location

Instituto Oftalmologico Gómez-Ulla

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Rio Hortega

Valladolid, 47006, Spain

Location

Moorfields Eye Hospital NHS Foundation Trust

London, England, EC1V 2PD, United Kingdom

Location

Eye Clinic, Acre Mill Outpatients, Huddersfield Royal Infirmary

Huddersfield, West Yorkshire, HD3 3EA, United Kingdom

Location

Bristol Eye Hospital

Bristol, BS1 2LX, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LEI 5WW, United Kingdom

Location

London North West University Hospital Trust

London, NW10 7NS, United Kingdom

Location

King's College Hospital NHS Trust

London, SE5 9RS, United Kingdom

Location

Oxford Eye Hospital

Oxford, OX3 9DU, United Kingdom

Location

Salisbury NHS Foundation Trust

Salisbury, SP2 8BJ, United Kingdom

Location

Sunderland Eye Infirmary

Sunderland, SR2 9HP, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 40388106 DERIVED

• 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.

  PMID: 40280279 DERIVED

• 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.

  PMID: 38722644 DERIVED

• 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.

  PMID: 37865470 DERIVED

• 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.

  PMID: 37314061 DERIVED

MeSH Terms

Conditions

Geographic Atrophy

Condition Hierarchy (Ancestors)

Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases

Results Point of Contact

• Title: Apellis Clinical Trial Information Line
• Organization: Apellis Pharmaceuticals, Inc

clinicaltrials@apellis.com

1-833-284-6361

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 15, 2018
• Study Start: August 31, 2018
• Primary Completion: June 21, 2021
• Study Completion: June 20, 2022
• Last Updated: June 18, 2023
• Results First Posted: June 18, 2023

Record last verified: 2023-05

Locations

DE (6); PL (4); AR (10); IL (6); PR (1); GB (10); CA (4); ES (3); BR (6); CZ (4); FR (7); AU (3); US (73); IT (2); NZ (2)