Clinical trial NCT03525600: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Geographic Atrophy
Lead sponsor: Apellis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-05-15
Enrollment: 621
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12
timeFrame: Baseline (screening) and Month 12
Secondary outcomes:
measure: LS Mean Change From Baseline in the Total Area of GA Lesions in the Study Eye at Month 24
timeFrame: Baseline (screening) and Month 24
measure: Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24
timeFrame: From Baseline (screening) through Month 24
measure: LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24
timeFrame: Baseline (screening) and Month 24
measure: LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24
timeFrame: Baseline (screening) and Month 24
measure: LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24
timeFrame: Baseline (screening) and Month 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retinal Research Institute
state: Arizona
city: Phoenix
country: United States
facility: Associated Retina Consultants, Ltd
state: Arizona
city: Arcadia
country: United States
facility: Retina Institute of California dba Acuity Eye Grp
state: California
city: Bakersfield
country: United States
facility: California Retina Consultants
state: California
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates Medical Group
state: California
city: Encino
country: United States
facility: The Retina Partners
state: California
city: Irvine
country: United States
facility: The Gavin Herbert Eye Institute/UC Irvine
state: California
city: Mountain View
country: United States
facility: Northern California Retina Vitreous Associates
state: California
city: Palm Desert
country: United States
facility: Retina Institute of California Medical Group
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Standford, Stanford School of Medicine
state: California
city: Poway
country: United States
facility: Retina Consultants San Diego
state: California
city: Redlands
country: United States
facility: Retina Consultants of Southern California
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Walnut Creek
country: United States
facility: Bay Area Retina Associates
state: California
city: Danbury
country: United States
facility: Danbury Eye Physicians & Surgeons, P.C. - Danbury
state: Connecticut
city: Hamden
country: United States
facility: New England Retina Associates
state: Connecticut
city: Waterford
country: United States
facility: Retina Group of New England,PC
state: Connecticut
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Institute, Inc.
state: Florida
city: Fort Lauderdale
country: United States
facility: Pinnacle Research Institute
state: Florida
city: Fort Myers
country: United States
facility: Retina Health Center
state: Florida
city: Palm Beach Gardens
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Pinellas Park
country: United States
facility: Eye Associates of Pinellas
state: Florida
city: Stuart
country: United States
facility: East Florida Eye Institute
state: Florida
city: Tallahassee
country: United States
facility: Southern Vitreoretinal Associates
state: Florida
city: Tampa
country: United States
facility: Retina Associates of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida (USF) Eye Institute
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina
state: Georgia
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Leawood
country: United States
facility: Sabates Eye Center
state: Kansas
city: Baltimore
country: United States
facility: Elman Retina Group, PA
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants, PC
state: Maryland
city: Hagerstown
country: United States
facility: Mid Atlantic Retina Specialists
state: Maryland
city: Towson
country: United States
facility: Retina Specialists
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Springfield
country: United States
facility: New England Retina Consultants, PC
state: Massachusetts
city: Grand Rapids
country: United States
facility: Associated Retinal Consultants, P.C
state: Michigan
city: Grand Rapids
country: United States
facility: Retina Specialists of Michigan / Foundation for Vision
state: Michigan
city: Southfield
country: United States
facility: Retina Consultants of Michigan
state: Michigan
city: Traverse City
country: United States
facility: Associated Retinal Consultants PC
state: Michigan
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Teaneck
country: United States
facility: Retina Associates of New Jersey (NJ Retina)
state: New Jersey
city: Great Neck
country: United States
facility: Long Island Vitreoretinal Consultants
state: New York
city: New York
country: United States
facility: Vitreous Retina Macula Consultants of NY
state: New York
city: Asheville
country: United States
facility: Western Carolina Retinal Associates
state: North Carolina
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose and Throat Associates, PS
state: North Carolina
city: Hickory
country: United States
facility: Graystone Eye
state: North Carolina
city: Cleveland
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Retina Associates of Cleveland, Inc
state: Ohio
city: Cleveland
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, Cole Eye Institute
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Youngstown
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Portland
country: United States
facility: Retina Northwest, PC
state: Oregon
city: Portland
country: United States
facility: Eye Health Northwest
state: Oregon
city: Philadelphia
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Retina, PC
state: Tennessee
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Amarillo
country: United States
facility: Southwest Retina Specialists
state: Texas
city: Austin
country: United States
facility: Retina Consultants of Austin (Retina Research Center)
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston, PA
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute, PA
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston
state: Texas
city: Murray
country: United States
facility: Retina Associates of Utah, PC
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: The Retina Group of Washington
state: Virginia
city: Warrenton
country: United States
facility: Virginia Retina Center
state: Virginia
city: Bellevue
country: United States
facility: Vitreoretinal Associates of Washington
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Fundacion Zambrano
state: Capital Federal
city: Rosario
country: Argentina
facility: Microcirugia Ocular
state: Corrientes
city: Rosario
country: Argentina
facility: Grupo Laser Vision
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Organizacion Medica de investigacion
city: Buenos Aires
country: Argentina
facility: Centro Oftalmologico Dr Charles
city: Buenos Aires
country: Argentina
facility: Diagnostico Ocular
city: Córdoba
country: Argentina
facility: Centro Privado de Ojos Romagosa SA
city: Córdoba
country: Argentina
facility: Instituto Oftalmologico de Cordoba
city: Mendoza
country: Argentina
facility: Oftar Mendoza SRL
city: Rosario
country: Argentina
facility: Oftalmologos Especialistas
city: Sydney
country: Australia
facility: Sydney Retina
state: New South Wales
city: East Melbourne
country: Australia
facility: Centre for Eye Research Australia
state: Victoria
city: Hurstville
country: Australia
facility: Retina and Eye Consultants
city: Vitória
country: Brazil
facility: Clinica Ocular Oftalmologia LTDA
state: Espirito Santo
city: Osasco
country: Brazil
facility: Clinica Oftalmologica Sao Lucas
state: Sao Paulo
city: São Paulo
country: Brazil
facility: IPEPO - Instituto Da Visao
state: Vila Clementino
city: Belo Horizonte
country: Brazil
facility: Instituto da Visão - Hospital de Olhos Ltda
city: Porto Alegre
country: Brazil
facility: Hospital De Clinicas De Porto Alegre
city: São Paulo
country: Brazil
facility: UNIFESP - Federal University
city: London
country: Canada
facility: Ivey Eye Institute
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Eye Institute
state: Ontario
city: Toronto
country: Canada
facility: DRY AMD Clinic - St. Michael's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Retina Centre of Ottawa
city: Ostrava-Poruba
country: Czechia
facility: Fakultní nemocnice Ostrava
city: Pardubice
country: Czechia
facility: OFTEX Eye Clinic
city: Praha
country: Czechia
facility: AXON Clinical, S.R.O.
city: Vinohrady
country: Czechia
facility: University Hospital Kralovske Vinochrady
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Lyon
country: France
facility: Hopital de la Croix-Rousse
city: Marseille
country: France
facility: Centre Monticelli Paradis
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Paris
country: France
facility: Centre Ophtalmologique de l´Odéon
city: Saint-Cyr-sur-Loire
country: France
facility: Centre Ophthalmologique Saint-Exupery
city: Strasbourg
country: France
facility: Maison Rouge Ophthalmologic Center
city: Bonn
country: Germany
facility: Universitäts-Augenklinik Bonn
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen gGmbH
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah tikva
country: Israel
facility: Rabin Medical Center
city: Reẖovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Luigi Sacco Hospital
city: Auckland
country: New Zealand
facility: Retina Specialist
city: Hamilton
country: New Zealand
facility: Hamilton Eye Clinic
city: Bydgoszcz
country: Poland
facility: Oftalmika Eye Hospital
city: Olsztyn
country: Poland
facility: Centrum Diagnostyki i Mikrochirurgii Oka - LENS
city: Tarnow
country: Poland
facility: Centrum Medyczne UNO-MED
city: Łódź
country: Poland
facility: Jasne Blonia Eye Clinic
city: Arecibo
country: Puerto Rico
facility: Emanuelli Research and Development Center
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Santiago De Compostela
country: Spain
facility: Instituto Oftalmologico Gómez-Ulla
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
state: England
city: Huddersfield
country: United Kingdom
facility: Eye Clinic, Acre Mill Outpatients, Huddersfield Royal Infirmary
state: West Yorkshire
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Leeds
country: United Kingdom
facility: St James's University Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: London North West University Hospital Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Trust
city: Oxford
country: United Kingdom
facility: Oxford Eye Hospital
city: Salisbury
country: United Kingdom
facility: Salisbury NHS Foundation Trust
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
Study officials:
References: