Clinical trial NCT03525613: 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
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: 637
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.
* 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
  * 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 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.
* 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.
* 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 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 Mean Threshold Sensitivity of All Points of the Study Eye at Month 24
timeFrame: Baseline (screening) and 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: Arizona Retina & Vitreous Consultants
state: Arizona
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: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: Huntington Beach
country: United States
facility: Atlantis Eyecare
state: California
city: La Jolla
country: United States
facility: University of California, San Diego, Jacobs Retina
state: California
city: Palo Alto
country: United States
facility: Byers Eye Institute at Stanford, Stanford School of Medicine
state: California
city: Pasadena
country: United States
facility: Doheny Eye Center UCLA
state: California
city: Poway
country: United States
facility: Retina Consultants San Diego
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Med Group, Inc.
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Medical Group
state: California
city: Santa Barbara
country: United States
facility: California Retina Consultants
state: California
city: Durango
country: United States
facility: Southwest Retina Research Center, LLC
state: Colorado
city: Golden
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Clearwater
country: United States
facility: Blue Ocean Clinical Research / The Macula Center
state: Florida
city: Fort Myers
country: United States
facility: National Ophthalmic Research Institute (Retina Consultants of Southwest Florida)
state: Florida
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Naples
country: United States
facility: Bascom Palmer Eye Institute of Naples
state: Florida
city: Pensacola
country: United States
facility: Retina Specialty Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Bloomington
country: United States
facility: Gailey Eye Clinic Retina Center
state: Illinois
city: Chicago
country: United States
facility: Northwestern Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Lexington
country: United States
facility: Retina and Vitreous Associates of Kentucky, PSC dba Retina Associates of Kentucky
state: Kentucky
city: Metairie
country: United States
facility: Retina Associates New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: The Retina Care Center
state: Maryland
city: Chevy Chase
country: United States
facility: The Retina Group of Washington
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Center
state: Maryland
city: Hagerstown
country: United States
facility: Mid Atlantic Retina Specialists
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: New England Retina Consultants
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine Kellogg Eye Center
state: Michigan
city: Grand Rapids
country: United States
facility: Associated Retinal Consultants, P.C
state: Michigan
city: Minneapolis
country: United States
facility: VitreoRetinal Surgery PA
state: Minnesota
city: Reno
country: United States
facility: Sierra Eye Associates
state: Nevada
city: Bloomfield
country: United States
facility: Retina Center of NJ, LLC
state: New Jersey
city: Toms River
country: United States
facility: NJ Retina
state: New Jersey
city: Albuquerque
country: United States
facility: Vision Research Center Eye Associates of NM
state: New Mexico
city: Lynbrook
country: United States
facility: Ophthalmic Consultants of Long Island
state: New York
city: New York
country: United States
facility: New York Eye and Ear Infirmary of Mount Sinai
state: New York
city: New York
country: United States
facility: Vitreous Retina Macula Consultants of NY
state: New York
city: Durham
country: United States
facility: Duke University, Duke Eye Center
state: North Carolina
city: Edmond
country: United States
facility: Research - Retina Vitreous Center
state: Oklahoma
city: Eugene
country: United States
facility: Oregon Retina, LLP
state: Oregon
city: Bethlehem
country: United States
facility: Mid Atlantic Retina
state: Pennsylvania
city: Monroeville
country: United States
facility: Retina Vitreous Consultants
state: Pennsylvania
city: Philadelphia
country: United States
facility: Mid Atlantic Retina, Wills Eye Hospital
state: Pennsylvania
city: West Mifflin
country: United States
facility: AIO Visionary Eye Care
state: Pennsylvania
city: Germantown
country: United States
facility: Charles Retina Institute
state: Tennessee
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: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Houston
country: United States
facility: Houston Eye Associates
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston, PA
state: Texas
city: San Antonio
country: United States
facility: San Antonia Eye Center
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: San Antonio
country: United States
facility: Retina Associates of South Texas
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: San Antonio
country: United States
facility: Brown Retina Institute
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research Group
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - John A. Moran Center
state: Utah
city: Falls Church
country: United States
facility: Emerson Clinical Research Institute
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Parramatta
country: Australia
facility: Marsden Eye Specialist
state: New South Wales
city: Adelaide
country: Australia
facility: Adelaide Eye & Retina Clinic
state: South Australia
city: Sydney
country: Australia
facility: Save Sight Institute
state: South Block
city: Nedlands
country: Australia
facility: Lions Eye Institute
state: Western Australia
city: Strathfield
country: Australia
facility: Strathfield Retina Clinic
city: Westmead
country: Australia
facility: Sydney West Retina
city: São Paulo
country: Brazil
facility: UNIFESP - Federal University
city: Toronto
country: Canada
facility: UHN Toronto Western Hospital
state: Ontario
city: Praha
country: Czechia
facility: AXON Clinical S.R.O
city: Zlín
country: Czechia
facility: Gemini Eye Clinic
city: Bordeaux
country: France
facility: CHU Dijon
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Paris
country: France
facility: Hopital Lariboisière
city: Paris
country: France
facility: CHNO des Quinze-Vingts
city: Paris
country: France
facility: Centre Ophtalmologique d'Imagerie et Laser
city: Strasbourg
country: France
facility: CHU de Strasbourg Hopital Civil
city: Écully
country: France
facility: Clinique du Val d'Ouest
city: Bonn
country: Germany
facility: Universitäts-Augenklinik Bonn
city: Freiburg im Breisgau
country: Germany
facility: University Opthalmology Clinic
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen Georg-August-Universität
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Augenklinik der LMU München
city: Münster
country: Germany
facility: Augenzentrum am St. Franziskus-Hospital
city: Münster
country: Germany
facility: Universitäts-Augenklinik
city: Tübingen
country: Germany
facility: STZ Eyetrial
city: Haifa
country: Israel
facility: Rambam Medical Centre
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: Luigi Sacco Hospital
city: Roma
country: Italy
facility: IRCCS Fondazione G.B. Bietti
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center Oogheelkunde
city: Christchurch
country: New Zealand
facility: Southern Eye Specialists
city: Bydgoszcz
country: Poland
facility: Oculomedica Eye Centre
city: Bydgoszcz
country: Poland
facility: Oftalmika Eye Hospital
city: Rzeszów
country: Poland
facility: Eye Surgery Center Professor Zagorski
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro
state: Madrir
city: Barcelona
country: Spain
facility: Centro Médico Teknon
city: Barcelona
country: Spain
facility: Centro de Oftalmologia Barraquer
city: Belfast
country: United Kingdom
facility: The Royal Victoria Hospital
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals NHS Foundation Trust
city: Sunderland
country: United Kingdom
facility: Sunderland Eye Infirmary
city: York
country: United Kingdom
facility: York Teaching Hospital NHS Foundation Trust
Study officials:
References: