Study of Pegcetacoplan (APL-2) Therapy in Patients With Geographic Atrophy

NCT02503332 | Completed Phase 2 Results DMC

• 1 other identifier: POT-CP121614
• Study Type: interventional
• Target: 246
• Locations: 3 countries
• Sites: 46

Brief Summary

The primary objectives of the study are to assess the safety, tolerability and evidence of activity of multiple intravitreal (IVT) injections of pegcetacoplan in subjects with Geographic Atrophy associated with Age-Related Macular Degeneration (AMD).

Conditions

Geographic Atrophy

Outcome Measures

Primary Outcomes (2)

• Least Square (LS) Mean Change From Baseline in Square Root GA Lesion Size in the Study Eye at Month 12

  The square root GA lesion size (i.e. transformed area of GA) was measured by FAF photographs. Baseline was defined as the last available, non-missing observation prior to first study drug administration.

  Baseline (screening) and Month 12.

• Number of Subjects With Treatment Emergent Adverse Events (TEAEs) in the Study Eye, Including by Severity

  A TEAE was defined as any adverse event (AE) that commenced or worsened on or after time of first study drug administration up to 60 days beyond last dose of study drug. A treatment-related TEAE was defined as a TEAE with a relationship to study drug of possibly related or probably related or not reported. Severity of TEAEs were categorized as mild; moderate; severe; life-threatening or death related to TEAE, according to Common Terminology Criteria for AEs v4.03. A TEAE of special interest (TEAESI) was defined as a TEAE of scientific and medical concern specific to pegcetacoplan, whether serious or non-serious.

  From the time of first study drug administration (Day 1) up to Month 12 (Data cut-off date).

Secondary Outcomes (6)

• LS Mean Change From Baseline in Untransformed GA Lesion Size in the Study Eye at Month 12

  Baseline (Day 1) and Month 12.

• LS Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score of the Study Eye at Month 12

  Baseline (Day 1) and Month 12.

• LS Mean Change From Baseline in Low Luminance BCVA (LL-BCVA) Score in the Study Eye at Month 12

  Baseline (Day 1) and Month 12.

• LS Mean Change From Baseline in Low Luminance VA (LL-VA) Deficit Score in the Study Eye at Month 12

  Baseline (Day 1) and Month 12.

• LS Mean Change From Baseline in Distance of GA Lesion From the Fovea (Foveal Encroachment) in the Study Eye at Month 12

  Baseline (Day 1) and Month 12.

Study Arms (4)

Pegcetacoplan 15 mg/100 µL Monthly for 12 months

EXPERIMENTAL

A single dose of 15 mg pegcetacoplan/100 µL will be administered via intravitreal injection in this study. Subjects will receive an injection every month for 12 consecutive months.

Drug: Pegcetacoplan

Pegcetacoplan 15 mg/100 µL EOM for 12 months

EXPERIMENTAL

A single dose of 15 mg pegcetacoplan/100 µL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month (EOM) for 12 consecutive months.

Drug: Pegcetacoplan

Sham Monthly for 12 months

SHAM COMPARATOR

Subjects will receive a Sham procedure every month for 12 consecutive months.

Other: Sham Procedure

Sham EOM for 12 months

SHAM COMPARATOR

Subjects will receive a Sham procedure every other month (EOM) for 12 consecutive months.

Other: Sham Procedure

Interventions

Pegcetacoplan DRUG

Also known as: APL-2

Pegcetacoplan 15 mg/100 µL EOM for 12 months; Pegcetacoplan 15 mg/100 µL Monthly for 12 months

Sham Procedure OTHER

Sham EOM for 12 months; Sham Monthly for 12 months

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female.
• Age greater than or equal to 50 years.
• BCVA of 20/320 (Snellen equivalent) or better using ETDRS charts.
• Diagnosis of GA of the macula secondary to age-related macular degeneration, confirmed within 14 days prior to randomization by the central reading center (CRC) using Fundus Autofluorescence (FAF) images, as well as the following criteria:
• Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas \[DA\] respectively), determined by screening images of FAF.
• If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA).
• GA can be completely visualized on the macula centered image.
• GA must be able to be photographed in its entirety.
• GA must be able to be measured separately from any areas of peripapillary atrophy as assessed by the CRC.
• 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.
• 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.

You may not qualify if:

• GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy.
• Spherical equivalent of the refractive error demonstrating \> 6 diopters of myopia or an axial length \>26 mm.
• Any history or current evidence of exudative ("wet") AMD including any evidence of retinal pigment epithelium rips or evidence of neovascularization anywhere in the retina based on fluorescein angiogram as assessed by the CRC.
• Any ophthalmologic condition that reduces the clarity of the media and that, in the opinion of the Investigator interferes with ophthalmologic examination (e.g. advanced cataract or corneal abnormalities).
• Any ophthalmologic condition that prevents adequate imaging of the retina judged by the site or CRC.
• Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.
• Aphakia or absence of the posterior capsule. Previous violation of the posterior capsule is also excluded unless it occurred as a result of yttrium aluminum garnet (YAG) laser posterior capsulotomy in association with prior posterior chamber intraocular lens implantation and at least 60 days prior to Day 0.
• Any ophthalmic condition that may require surgery during the study period.
• Any contraindication to IVT injection including current ocular or periocular infection.
• History of uveitis or endophthalmitis.
• History of IVT injection at any time.
• Medical or psychiatric conditions that, in the opinion of the investigator, make consistent follow-up over the treatment period unlikely, or in general a poor medical risk because of other systemic diseases or active uncontrolled infections.
• 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.
• Hypersensitivity to fluorescein.

Sponsors & Collaborators

• Apellis Pharmaceuticals, Inc.: lead

Study Sites (46)

Retina Speciality Institute

Mobile, Alabama, 36606, United States

Location

Retinal Research Institute

Phoenix, Arizona, 85014, United States

Location

Retina Vitreous Asociates Mdical Goup

Beverly Hills, California, 90211, United States

Location

The Gavin Herbert Eye Institute/UC Irvine

Irvine, California, 92697, United States

Location

University of Southern California - USC Eye Institute

Los Angeles, California, 90033, United States

Location

Byers Eye Institute at Stanford, Stanford School of Medicine

Palo Alto, California, 94303, United States

Location

New England Retina Associates

New London, Connecticut, 06320, United States

Location

Florida Eye Microsurgical Institute, Inc.

Boynton Beach, Florida, 33426, United States

Location

Retina Health Center

Fort Myers, Florida, 33907, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

South East Retina

Augusta, Georgia, 30909, United States

Location

Illinois Retina Associates

Harvey, Illinois, 60426, United States

Location

Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

Location

Elman Research

Baltimore, Maryland, 21237, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Associated Retinal Consultants PC

Grand Rapids, Michigan, 45946, United States

Location

Associated Retinal Consultants, PC

Traverse City, Michigan, 49586, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Eyesight Opthalmic Services PA

Portsmouth, New Hampshire, 03801, United States

Location

Vitreous Retina Macula Consultants of New York

New York, New York, 10022, United States

Location

Charlotte Eye Ear Nose and Throat Associates

Charlotte, North Carolina, 28210, United States

Location

Duke University, Duke Eye Center

Durham, North Carolina, 27705, United States

Location

Charlotte Eye Ear Nose and Throat Associates

Statesville, North Carolina, 28677, United States

Location

Cleveland Clinic Foundation/ Cole Eye Institute

Cleveland, Ohio, 44106, United States

Location

Retina Associates of Cleveland

Cleveland, Ohio, 44122, United States

Location

Mid Atlantic

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

Retina Research Center

Austin, Texas, 78705, United States

Location

Retina Consultants of Houston

Houston, Texas, 77030, United States

Location

Valley Retina Institute, PA

McAllen, Texas, 75803, United States

Location

Retina Specialists

Plano, Texas, 75093, United States

Location

Retina Consultants of Houston (The Woodlands)

The Woodlands, Texas, 77384, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Marsden Eye Specialists

Paramatta, New South Wales, 2150, Australia

Location

Save Sight Institute, Sydney Eye Hospital

Sydney, New South Wales, 2000, Australia

Location

Sydney Retina Clinic and Day Surgery

Sydney, New South Wales, 2000, Australia

Location

Sydney West Retina

Westmead, New South Wales, 2145, Australia

Location

Hobart eye Surgeons

Hobart, Tasmania, 7002, Australia

Location

Tasmanian Eye Institute

South Launceston, Tasmania, 7249, Australia

Location

Royal Victorian Eye and Ear Hospital

East Melbourne, Victoria, 3002, Australia

Location

Center for Eye Research Australia

Melbourne, Victoria, 3002, Australia

Location

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Auckland Eye

Remuera, Auckland, 1050, New Zealand

Location

Southern Eye Specialists

Merivale, Christchurch, 8014, New Zealand

Location

Related Publications (7)

• Reiter GS, Lachinov D, Buhl W, Weigert G, Grechenig C, Mai J, Bogunovic H, Schmidt-Erfurth U. A Novel Management Challenge in Age-Related Macular Degeneration: Artificial Intelligence and Expert Prediction of Geographic Atrophy. Ophthalmol Retina. 2025 May;9(5):421-430. doi: 10.1016/j.oret.2024.10.029. Epub 2024 Nov 9.

  PMID: 39522752 DERIVED

• Fu DJ, Lipkova V, Liefers B, Glinton S, Faes L, McKeown A, Scheibler L, Pontikos N, Patel PJ, Zhang G, Keane PA, Balaskas K. Evaluating the Effects of C3 Inhibition on Geographic Atrophy Progression from Deep-Learning OCT Quantification: A Split-Person Study. Ophthalmol Ther. 2023 Dec;12(6):3143-3158. doi: 10.1007/s40123-023-00798-7. Epub 2023 Sep 16.

  PMID: 37715860 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

• Pfau M, Schmitz-Valckenberg S, Ribeiro R, Safaei R, McKeown A, Fleckenstein M, Holz FG. Association of complement C3 inhibitor pegcetacoplan with reduced photoreceptor degeneration beyond areas of geographic atrophy. Sci Rep. 2022 Oct 25;12(1):17870. doi: 10.1038/s41598-022-22404-9.

  PMID: 36284220 DERIVED

• Vogl WD, Riedl S, Mai J, Reiter GS, Lachinov D, Bogunovic H, Schmidt-Erfurth U. Predicting Topographic Disease Progression and Treatment Response of Pegcetacoplan in Geographic Atrophy Quantified by Deep Learning. Ophthalmol Retina. 2023 Jan;7(1):4-13. doi: 10.1016/j.oret.2022.08.003. Epub 2022 Aug 7.

  PMID: 35948209 DERIVED

• Liao DS, Metlapally R, Joshi P. Pegcetacoplan treatment for geographic atrophy due to age-related macular degeneration: a plain language summary of the FILLY study. Immunotherapy. 2022 Sep;14(13):995-1006. doi: 10.2217/imt-2022-0078. Epub 2022 Jul 21.

  PMID: 35860926 DERIVED

• Nittala MG, Metlapally R, Ip M, Chakravarthy U, Holz FG, Staurenghi G, Waheed N, Velaga SB, Lindenberg S, Karamat A, Koester J, Ribeiro R, Sadda S. Association of Pegcetacoplan With Progression of Incomplete Retinal Pigment Epithelium and Outer Retinal Atrophy in Age-Related Macular Degeneration: A Post Hoc Analysis of the FILLY Randomized Clinical Trial. JAMA Ophthalmol. 2022 Mar 1;140(3):243-249. doi: 10.1001/jamaophthalmol.2021.6067.

  PMID: 35113137 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

Study Officials

• Federico Grossi, MD PhD

  Apellis Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 20, 2015
• Study Start: September 24, 2015
• Primary Completion: July 14, 2017
• Study Completion: January 17, 2018
• Last Updated: October 6, 2020
• Results First Posted: October 6, 2020

Record last verified: 2020-09

Locations

AU (9); NZ (2); US (35)