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

NCT03525613 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: APL2-304
• Study Type: interventional
• Target: 637
• Locations: 14 countries
• Sites: 112

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 (6)

• LS Mean Change From Baseline in 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 Mean Threshold Sensitivity of All Points of the Study Eye at Month 24

  Baseline (screening) and 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

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 monthly 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

Also known as: Pegcetacoplan

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.
• 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

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.
• 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.
• 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 (112)

Arizona Retina & Vitreous Consultants

Phoenix, Arizona, 85021, United States

Location

California Retina Consultants

Bakersfield, California, 93309, United States

Location

Retina Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

Retinal Diagnostic Center

Campbell, California, 95508, United States

Location

Retina Consultants of Orange County

Fullerton, California, 92835, United States

Location

Atlantis Eyecare

Huntington Beach, California, 92647, United States

Location

University of California, San Diego, Jacobs Retina

La Jolla, California, 92093, United States

Location

Byers Eye Institute at Stanford, Stanford School of Medicine

Palo Alto, California, 94303, United States

Location

Doheny Eye Center UCLA

Pasadena, California, 91105, United States

Location

Retina Consultants San Diego

Poway, California, 92064, United States

Location

Retinal Consultants Med Group, Inc.

Sacramento, California, 95819, United States

Location

Orange County Retina Medical Group

Santa Ana, California, 92705, United States

Location

California Retina Consultants

Santa Barbara, California, 93103, United States

Location

Southwest Retina Research Center, LLC

Durango, Colorado, 81301, United States

Location

Colorado Retina Associates

Golden, Colorado, 80401, United States

Location

Retina Group of New England

Waterford, Connecticut, 06385, United States

Location

Blue Ocean Clinical Research / The Macula Center

Clearwater, Florida, 33761, United States

Location

National Ophthalmic Research Institute (Retina Consultants of Southwest Florida)

Fort Myers, Florida, 33912, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Bascom Palmer Eye Institute of Naples

Naples, Florida, 34103, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Center for Retina and Macular Disease

Winter Haven, Florida, 33880, United States

Location

Southeast Retina Center, PC

Augusta, Georgia, 30909, United States

Location

Gailey Eye Clinic Retina Center

Bloomington, Illinois, 61704, United States

Location

Northwestern Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

Location

Retina and Vitreous Associates of Kentucky, PSC dba Retina Associates of Kentucky

Lexington, Kentucky, 40509, United States

Location

Retina Associates New Orleans

Metairie, Louisiana, 70006, United States

Location

The Retina Care Center

Baltimore, Maryland, 21209, United States

Location

The Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Cumberland Valley Retina Center

Hagerstown, Maryland, 21740, United States

Location

Mid Atlantic Retina Specialists

Hagerstown, Maryland, 21740, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02116, United States

Location

New England Retina Consultants

Springfield, Massachusetts, 01107, United States

Location

Michigan Medicine Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Associated Retinal Consultants, P.C

Grand Rapids, Michigan, 49564, United States

Location

VitreoRetinal Surgery PA

Minneapolis, Minnesota, 55435, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Retina Center of NJ, LLC

Bloomfield, New Jersey, 07003, United States

Location

NJ Retina

Toms River, New Jersey, 08755, United States

Location

Vision Research Center Eye Associates of NM

Albuquerque, New Mexico, 87109, United States

Location

Ophthalmic Consultants of Long Island

Lynbrook, New York, 11563, United States

Location

New York Eye and Ear Infirmary of Mount Sinai

New York, New York, 10003, United States

Location

Vitreous Retina Macula Consultants of NY

New York, New York, 10022, United States

Location

Duke University, Duke Eye Center

Durham, North Carolina, 27710, United States

Location

Research - Retina Vitreous Center

Edmond, Oklahoma, 73013, United States

Location

Oregon Retina, LLP

Eugene, Oregon, 97405, United States

Location

Mid Atlantic Retina

Bethlehem, Pennsylvania, 18017, United States

Location

Retina Vitreous Consultants

Monroeville, Pennsylvania, 15146, United States

Location

Mid Atlantic Retina, Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

AIO Visionary Eye Care

West Mifflin, Pennsylvania, 15122, United States

Location

Charles Retina Institute

Germantown, Tennessee, 38138, United States

Location

Tennessee Retina, PC

Nashville, Tennessee, 37203, United States

Location

Retina Research Institute of Texas

Abilene, Texas, 79606, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Houston Eye Associates

Houston, Texas, 77025, United States

Location

Retina Consultants of Houston, PA

Houston, Texas, 77030, United States

Location

San Antonia Eye Center

San Antonio, Texas, 78215, United States

Location

Medical Center Ophthalmology Associates

San Antonio, Texas, 78240, United States

Location

Retina Associates of South Texas

San Antonio, Texas, 78240, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

Brown Retina Institute

San Antonio, Texas, 78251, United States

Location

Strategic Clinical Research Group

Willow Park, Texas, 76087, United States

Location

University of Utah - John A. Moran Center

Salt Lake City, Utah, 84132, United States

Location

Emerson Clinical Research Institute

Falls Church, Virginia, 22046, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Marsden Eye Specialist

Parramatta, New South Wales, 2150, Australia

Location

Adelaide Eye & Retina Clinic

Adelaide, South Australia, 5000, Australia

Location

Save Sight Institute

Sydney, South Block, 2000, Australia

Location

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Strathfield Retina Clinic

Strathfield, 2135, Australia

Location

Sydney West Retina

Westmead, 2145, Australia

Location

UNIFESP - Federal University

São Paulo, 04021-001, Brazil

Location

UHN Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

AXON Clinical S.R.O

Prague, 150 00, Czechia

Location

Gemini Eye Clinic

Zlín, 76001, Czechia

Location

CHU Dijon

Bordeaux, 21 079, France

Location

CHU de Bordeaux

Bordeaux, 33076, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

Location

Clinique du Val d'Ouest

Écully, 69130, France

Location

Hopital Lariboisière

Paris, 75010, France

Location

CHNO des Quinze-Vingts

Paris, 75012, France

Location

Centre Ophtalmologique d'Imagerie et Laser

Paris, 75015, France

Location

CHU de Strasbourg Hopital Civil

Strasbourg, 67091, France

Location

Universitäts-Augenklinik Bonn

Bonn, 53127, Germany

Location

University Opthalmology Clinic

Freiburg im Breisgau, 79106, Germany

Location

Universitätsmedizin Göttingen Georg-August-Universität

Göttingen, 37075, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Augenklinik der LMU München

München, 80336, Germany

Location

Augenzentrum am St. Franziskus-Hospital

Münster, 48145, Germany

Location

Universitäts-Augenklinik

Münster, 48149, Germany

Location

STZ Eyetrial

Tübingen, 72076, Germany

Location

Rambam Medical Centre

Haifa, 3109601, Israel

Location

Carmel Medical Center

Haifa, 3436212, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Luigi Sacco Hospital

Milan, 20157, Italy

Location

IRCCS Fondazione G.B. Bietti

Roma, 128, Italy

Location

Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

Radboud University Medical Center Oogheelkunde

Nijmegen, 6525, Netherlands

Location

Southern Eye Specialists

Christchurch, 8013, New Zealand

Location

Oculomedica Eye Centre

Bydgoszcz, 85-316, Poland

Location

Oftalmika Eye Hospital

Bydgoszcz, 85-631, Poland

Location

Eye Surgery Center Professor Zagorski

Rzeszów, 35-017, Poland

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrir, 2822, Spain

Location

Centro Médico Teknon

Barcelona, 08022, Spain

Location

Centro de Oftalmologia Barraquer

Barcelona, 314, Spain

Location

The Royal Victoria Hospital

Belfast, BT12 6BA, United Kingdom

Location

Liverpool University Hospitals NHS Foundation Trust

Liverpool, L7 8XP, United Kingdom

Location

Sunderland Eye Infirmary

Sunderland, SR2 9HP, United Kingdom

Location

York Teaching Hospital NHS Foundation Trust

York, YO31 8HE, United Kingdom

Location

Related Publications (4)

• 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

• 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

Interventions

pegcetacoplan

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 28, 2021
• Study Completion: June 28, 2022
• Last Updated: July 6, 2023
• Results First Posted: July 6, 2023

Record last verified: 2023-06

Locations

IL (3); IT (3); US (67); FR (8); NL (2); DE (8); NZ (1); ES (3); CZ (2); GB (4); AU (6); PL (3); CA (1); BR (1)