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

NCT ID: NCT02503332

Last Updated: 2020-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 246 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-24
• Study Completion Date: 2018-01-17

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).

Detailed Description

This is a Phase II, prospective, multicenter, randomized, single-masked, sham-controlled study to assess the safety, tolerability and evidence of activity of multiple IVT injections of pegcetacoplan in subjects with GA secondary to Age-Related Macular Degeneration.

The study will randomize approximately 240 subjects to obtain at least 200 evaluable subjects across 40 multinational sites.

Subjects will be randomized in a 2:2:1:1 manner to receive pegcetacoplan Monthly (AM), pegcetacoplan Every-Other-Month (AEOM), Sham injection Monthly (SM) or Sham injection Every-Other-Month (SEOM), respectively.

All subjects will return to the clinical site on Day 7 to assess acute safety after the first injection. After that, subjects in the monthly groups will return to the clinical site for additional pegcetacoplan (or Sham) injections and study procedures every month until Month 12. Subjects in the Every-Other-Month groups will return to the clinical site for additional pegcetacoplan (or Sham) injections and study procedures every two months until Month 12. All subjects will return for follow-up visits on Months 15 and 18 (3 and 6 months after last injection, respectively).

Conditions

Geographic Atrophy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Pegcetacoplan 15 mg/100 µL Monthly for 12 months

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.

Group Type: EXPERIMENTAL

Pegcetacoplan

Intervention Type: DRUG

Pegcetacoplan 15 mg/100 µL EOM for 12 months

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.

Group Type: EXPERIMENTAL

Pegcetacoplan

Intervention Type: DRUG

Sham Monthly for 12 months

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

Group Type: SHAM_COMPARATOR

Sham Procedure

Intervention Type: OTHER

Sham EOM for 12 months

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

Group Type: SHAM_COMPARATOR

Sham Procedure

Intervention Type: OTHER

Interventions

Pegcetacoplan

Intervention Type: DRUG

Sham Procedure

Intervention Type: OTHER

Other Intervention Names

APL-2

Eligibility Criteria

Inclusion Criteria

1. Male or Female.

2. Age greater than or equal to 50 years.

3. BCVA of 20/320 (Snellen equivalent) or better using ETDRS charts.

4. 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:

1. Total GA area must be ≥ 2.5 and ≤ 17.5 mm2 (1 and 7 disk areas [DA] respectively), determined by screening images of FAF.

2. If GA is multifocal, at least one focal lesion must be ≥ 1.25 mm2 (0.5 DA).

3. GA can be completely visualized on the macula centered image.

4. GA must be able to be photographed in its entirety.

5. GA must be able to be measured separately from any areas of peripapillary atrophy as assessed by the CRC.

6. Presence of any pattern of hyperautofluorescence in the junctional zone of GA. Absence of hyperautoflouorescence (i.e. pattern = none) is exclusionary. See Holz et al. 2007.1

5. Female subjects must be:

1. Women of non-child-bearing potential (WONCBP), or

2. 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.

6. 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.

7. Willing and able to give informed consent.

1. GA due to causes other than AMD such as Stargardt disease, cone rod dystrophy or toxic maculopathies like plaquenil maculopathy.

2. Spherical equivalent of the refractive error demonstrating > 6 diopters of myopia or an axial length >26 mm.

3. 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.

4. Retinal disease other than AMD; however, benign conditions of the vitreous or peripheral retina are not exclusionary (i.e. pavingstone degeneration).

5. 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).

6. Any ophthalmologic condition that prevents adequate imaging of the retina judged by the site or CRC.

7. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization.

8. 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.

9. Any ophthalmic condition that may require surgery during the study period.

10. Any contraindication to IVT injection including current ocular or periocular infection.

11. History of uveitis or endophthalmitis.

12. History of IVT injection at any time.

13. Participation in another interventional clinical study, or use of any experimental treatment for AMD or any other investigational new drug within 6 weeks or 5 half-lives of the active (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.

14. 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.

15. 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.

16. Hypersensitivity to fluorescein.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Apellis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Federico Grossi, MD PhD

Role: STUDY_DIRECTOR

Apellis Pharmaceuticals, Inc.

Locations

Retina Speciality Institute

Mobile, Alabama, United States

Retinal Research Institute

Phoenix, Arizona, United States

Retina Vitreous Asociates Mdical Goup

Beverly Hills, California, United States

The Gavin Herbert Eye Institute/UC Irvine

Irvine, California, United States

University of Southern California - USC Eye Institute

Los Angeles, California, United States

Byers Eye Institute at Stanford, Stanford School of Medicine

Palo Alto, California, United States

New England Retina Associates

New London, Connecticut, United States

Florida Eye Microsurgical Institute, Inc.

Boynton Beach, Florida, United States

Retina Health Center

Fort Myers, Florida, United States

Bascom Palmer Eye Institute

Miami, Florida, United States

South East Retina

Augusta, Georgia, United States

Illinois Retina Associates

Harvey, Illinois, United States

Midwest Eye Institute

Indianapolis, Indiana, United States

Elman Research

Baltimore, Maryland, United States

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States

Associated Retinal Consultants PC

Grand Rapids, Michigan, United States

Associated Retinal Consultants, PC

Traverse City, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Eyesight Opthalmic Services PA

Portsmouth, New Hampshire, United States

Vitreous Retina Macula Consultants of New York

New York, New York, United States

Charlotte Eye Ear Nose and Throat Associates

Charlotte, North Carolina, United States

Duke University, Duke Eye Center

Durham, North Carolina, United States

Charlotte Eye Ear Nose and Throat Associates

Statesville, North Carolina, United States

Cleveland Clinic Foundation/ Cole Eye Institute

Cleveland, Ohio, United States

Retina Associates of Cleveland

Cleveland, Ohio, United States

Mid Atlantic

Philadelphia, Pennsylvania, United States

Black Hills Regional Eye Institute

Rapid City, South Dakota, United States

Tennessee Retina, PC

Nashville, Tennessee, United States

Retina Research Institute of Texas

Abilene, Texas, United States

Retina Research Center

Austin, Texas, United States

Retina Consultants of Houston

Houston, Texas, United States

Valley Retina Institute, PA

McAllen, Texas, United States

Retina Specialists

Plano, Texas, United States

Retina Consultants of Houston (The Woodlands)

The Woodlands, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Marsden Eye Specialists

Paramatta, New South Wales, Australia

Save Sight Institute, Sydney Eye Hospital

Sydney, New South Wales, Australia

Sydney Retina Clinic and Day Surgery

Sydney, New South Wales, Australia

Sydney West Retina

Westmead, New South Wales, Australia

Hobart eye Surgeons

Hobart, Tasmania, Australia

Tasmanian Eye Institute

South Launceston, Tasmania, Australia

Royal Victorian Eye and Ear Hospital

East Melbourne, Victoria, Australia

Center for Eye Research Australia

Melbourne, Victoria, Australia

Lions Eye Institute

Nedlands, Western Australia, Australia

Auckland Eye

Remuera, Auckland, New Zealand

Southern Eye Specialists

Merivale, Christchurch, New Zealand

Countries

United States; Australia; New Zealand

References

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.

Reference Type: DERIVED

PMID: 39522752 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37715860 (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)

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.

Reference Type: DERIVED

PMID: 36284220 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35948209 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35860926 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35113137 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

POT-CP121614

Identifier Type: -

Identifier Source: org_study_id