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

Geographic Atrophy Clinical Trial

Official title:

A Phase 3, Multi-Center, Randomized, Double-Masked, Sham-Controlled Study to Compare the Efficacy and Safety of Intravitreal Pegcetacoplan Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (AMD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03525600
• Other study ID #: APL2-303
• Status: Completed
• Phase: Phase 3
• Start date: August 31, 2018
• Est. completion date: June 20, 2022

Study information

• Verified date: May 2023
• Source: Apellis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 621
• Est. completion date: June 20, 2022
• Est. primary completion date: June 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

The study eye must meet all inclusion criteria. If both eyes meet the inclusion criteria, the eye with the worst visual acuity at the screening visit will be designated as the study eye. If both eyes have the same visual acuity, the right eye will be selected as the study eye.

Ocular- specific inclusion criteria apply to the study eye only, unless otherwise specified.

• 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:

Ocular specific exclusion criteria apply to the study eye only, unless otherwise specified.

• 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.

Related Conditions & MeSH terms

• Atrophy
• Geographic Atrophy
• Macular Degeneration

Intervention

Drug:
• APL-2
Complement (C3) Inhibitor
• APL-2
Complement (C3) Inhibitor

Other:
• Sham Procedure
Subjects will receive a Sham procedure every month
• Sham Procedure
Subjects will receive a Sham procedure every other month

Locations

Country	Name	City	State
Argentina	Centro Oftalmologico Dr Charles	Buenos Aires
Argentina	Diagnostico Ocular	Buenos Aires
Argentina	Fundacion Zambrano	Buenos Aires	Capital Federal
Argentina	Organizacion Medica de investigacion	Buenos Aires
Argentina	Centro Privado de Ojos Romagosa SA	Córdoba
Argentina	Instituto Oftalmologico de Cordoba	Córdoba
Argentina	Oftar Mendoza SRL	Mendoza
Argentina	Grupo Laser Vision	Rosario	Santa Fe
Argentina	Microcirugia Ocular	Rosario	Corrientes
Argentina	Oftalmologos Especialistas	Rosario
Australia	Centre for Eye Research Australia	East Melbourne	Victoria
Australia	Retina and Eye Consultants	Hurstville
Australia	Sydney Retina	Sydney	New South Wales
Brazil	Instituto da Visão - Hospital de Olhos Ltda	Belo Horizonte
Brazil	Clinica Oftalmologica Sao Lucas	Osasco	Sao Paulo
Brazil	Hospital De Clinicas De Porto Alegre	Porto Alegre
Brazil	IPEPO - Instituto Da Visao	São Paulo	Vila Clementino
Brazil	UNIFESP - Federal University	São Paulo
Brazil	Clinica Ocular Oftalmologia LTDA	Vitória	Espirito Santo
Canada	Ivey Eye Institute	London	Ontario
Canada	Retina Centre of Ottawa	Ottawa
Canada	University of Ottawa Eye Institute	Ottawa	Ontario
Canada	DRY AMD Clinic - St. Michael's Hospital	Toronto	Ontario
Czechia	Fakultní nemocnice Ostrava	Ostrava-Poruba
Czechia	OFTEX Eye Clinic	Pardubice
Czechia	AXON Clinical, S.R.O.	Praha
Czechia	University Hospital Kralovske Vinochrady	Vinohrady
France	Centre Hospitalier Intercommunal de Créteil	Créteil
France	Hopital de la Croix-Rousse	Lyon
France	Centre Monticelli Paradis	Marseille
France	CHU de Nantes - Hotel Dieu	Nantes
France	Centre Ophtalmologique de l´Odéon	Paris
France	Centre Ophthalmologique Saint-Exupery	Saint-Cyr-sur-Loire
France	Maison Rouge Ophthalmologic Center	Strasbourg
Germany	Universitäts-Augenklinik Bonn	Bonn
Germany	University Hospital Cologne	Cologne
Germany	Klinikum der Stadt Ludwigshafen gGmbH	Ludwigshafen
Germany	Klinikum rechts der Isar	München
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	University Hospital Würzburg	Würzburg
Israel	Shamir Medical Center	Be'er Ya'aqov
Israel	Rambam Medical Center	Haifa
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah tikva
Israel	Kaplan Medical Center	Re?ovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Luigi Sacco Hospital	Milano
Italy	Ospedale San Raffaele	Milano
New Zealand	Retina Specialist	Auckland
New Zealand	Hamilton Eye Clinic	Hamilton
Poland	Oftalmika Eye Hospital	Bydgoszcz
Poland	Jasne Blonia Eye Clinic	Lódz
Poland	Centrum Diagnostyki i Mikrochirurgii Oka - LENS	Olsztyn
Poland	Centrum Medyczne UNO-MED	Tarnow
Puerto Rico	Emanuelli Research and Development Center	Arecibo
Spain	Centro Médico Teknon	Barcelona
Spain	Instituto Oftalmologico Gómez-Ulla	Santiago De Compostela
Spain	Hospital Universitario Rio Hortega	Valladolid
United Kingdom	Bristol Eye Hospital	Bristol
United Kingdom	Eye Clinic, Acre Mill Outpatients, Huddersfield Royal Infirmary	Huddersfield	West Yorkshire
United Kingdom	St James's University Hospital	Leeds
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	King's College Hospital NHS Trust	London
United Kingdom	London North West University Hospital Trust	London
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London	England
United Kingdom	Oxford Eye Hospital	Oxford
United Kingdom	Salisbury NHS Foundation Trust	Salisbury
United Kingdom	Sunderland Eye Infirmary	Sunderland
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Southwest Retina Specialists	Amarillo	Texas
United States	Retina Institute of California dba Acuity Eye Grp	Arcadia	California
United States	Western Carolina Retinal Associates	Asheville	North Carolina
United States	Southeast Retina Center, PC	Augusta	Georgia
United States	Retina Consultants of Austin (Retina Research Center)	Austin	Texas
United States	California Retina Consultants	Bakersfield	California
United States	Elman Retina Group, PA	Baltimore	Maryland
United States	Vitreoretinal Associates of Washington	Bellevue	Washington
United States	Retina Vitreous Associates Medical Group	Beverly Hills	California
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Florida Eye Microsurgical Institute, Inc.	Boynton Beach	Florida
United States	Charlotte Eye Ear Nose and Throat Associates, PS	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic, Cole Eye Institute	Cleveland	Ohio
United States	Retina Associates of Cleveland	Cleveland	Ohio
United States	Retina Associates of Cleveland, Inc	Cleveland	Ohio
United States	Retina Associates of Cleveland, Inc.	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Danbury Eye Physicians & Surgeons, P.C. - Danbury	Danbury	Connecticut
United States	The Retina Partners	Encino	California
United States	The Retina Group of Washington	Fairfax	Virginia
United States	Pinnacle Research Institute	Fort Lauderdale	Florida
United States	Retina Health Center	Fort Myers	Florida
United States	Associated Retinal Consultants, P.C	Grand Rapids	Michigan
United States	Retina Specialists of Michigan / Foundation for Vision	Grand Rapids	Michigan
United States	Long Island Vitreoretinal Consultants	Great Neck	New York
United States	Cumberland Valley Retina Consultants, PC	Hagerstown	Maryland
United States	Mid Atlantic Retina Specialists	Hagerstown	Maryland
United States	New England Retina Associates	Hamden	Connecticut
United States	Graystone Eye	Hickory	North Carolina
United States	Retina Consultants of Houston, PA	Houston	Texas
United States	Midwest Eye Institute	Indianapolis	Indiana
United States	The Gavin Herbert Eye Institute/UC Irvine	Irvine	California
United States	Sabates Eye Center	Leawood	Kansas
United States	University of Wisconsin	Madison	Wisconsin
United States	Georgia Retina	Marietta	Georgia
United States	Valley Retina Institute, PA	McAllen	Texas
United States	Northern California Retina Vitreous Associates	Mountain View	California
United States	Retina Associates of Utah, PC	Murray	Utah
United States	Tennessee Retina, PC	Nashville	Tennessee
United States	Vitreous Retina Macula Consultants of NY	New York	New York
United States	Bascom Palmer Eye Institute	Palm Beach Gardens	Florida
United States	Retina Institute of California Medical Group	Palm Desert	California
United States	Byers Eye Institute at Standford, Stanford School of Medicine	Palo Alto	California
United States	Mid Atlantic Retina	Philadelphia	Pennsylvania
United States	Associated Retina Consultants, Ltd	Phoenix	Arizona
United States	Retinal Research Institute	Phoenix	Arizona
United States	Eye Associates of Pinellas	Pinellas Park	Florida
United States	Eye Health Northwest	Portland	Oregon
United States	Retina Northwest, PC	Portland	Oregon
United States	Retina Consultants San Diego	Poway	California
United States	Black Hills Regional Eye Institute	Rapid City	South Dakota
United States	Retina Consultants of Southern California	Redlands	California
United States	Sierra Eye Associates	Reno	Nevada
United States	Medical Center Ophthalmology Associates	San Antonio	Texas
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	California Retina Consultants	Santa Barbara	California
United States	Retina Consultants of Michigan	Southfield	Michigan
United States	Spokane Eye Clinical Research	Spokane	Washington
United States	New England Retina Consultants, PC	Springfield	Massachusetts
United States	East Florida Eye Institute	Stuart	Florida
United States	Southern Vitreoretinal Associates	Tallahassee	Florida
United States	Retina Associates of Florida	Tampa	Florida
United States	University of South Florida (USF) Eye Institute	Tampa	Florida
United States	Retina Associates of New Jersey (NJ Retina)	Teaneck	New Jersey
United States	Retina Consultants of Houston	The Woodlands	Texas
United States	Retina Specialists	Towson	Maryland
United States	Associated Retinal Consultants PC	Traverse City	Michigan
United States	Bay Area Retina Associates	Walnut Creek	California
United States	Virginia Retina Center	Warrenton	Virginia
United States	Retina Group of New England,PC	Waterford	Connecticut
United States	Retina Associates of Cleveland, Inc.	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Apellis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	LS Mean Change From Baseline in the Total Area of GA Lesions in the Study Eye at Month 24	The GA lesion area was measured by a quantified central reading center based on FAF images. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
Secondary	Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24	The mean change in GA lesion area through Month 24 was measured by assuming a piecewise linear trend in time with knots by FAF images at Months 6, 12, and 18 and was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	From Baseline (screening) through Month 24
Secondary	LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24	The maximum reading speed of the study eye was calculated per Minnesota Low-Vision Reading Test (MNREAD) or Radner Reading Charts user manuals, with no adjustment for reading inaccuracy. An additional step to cap resulting reading speed values at a maximum of 300 words per minute (wpm) was implemented. Maximum reading speed was calculated as the mean of the 3 highest non-zero reading speeds (or 2, or 1 value, as available), except when all wpm were calculated as 0 then the maximum reading speed was calculated as 0. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
Secondary	LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24	The FRI was an interviewer-administered questionnaire with 7 items on functional reading activities most relevant to GA AMD subjects. It had 1 total index score. For each FRI Index reading activity performed in the past 7 days, subjects were asked about the extent to which they required assistance beyond eyeglasses/contact lenses, including the use of low-vision aids, adjustments in the activity, or help from another subject. Mean FRI Index scores ranged from 1 (unable to do independently) to 4 (totally independent), with higher scores indicating higher functional reading independence. A negative change from baseline indicated a decrease in the FRI; disease worsening. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24
Secondary	LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24	The NL-BCVA was assessed by early treatment diabetic retinopathy study (ETDRS) chart prior to dilating the eyes at a starting distance of 4 meters and ranged from 0 (least score) to 100 (best score). If the 4-meter score was >19 letters read correctly, the visual acuity score was the sum of total letters correctly read at 4 meters plus the addition of 30. If the 4-meter score was =19 letters read correctly, the visual acuity score was the sum of total letters read correctly at 4 meters and total letters read correctly at the 1-meter distance. If no letters were read correctly at either the 4-meter distance or the 1-meter distance, the visual acuity score was 0. A positive change in the value indicated improvement in visual acuity. LS mean was calculated using a MMRM model. Baseline was defined as the last available, non-missing observation prior to first study drug administration.	Baseline (screening) and Month 24