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
- Conditions
- Geographic Atrophy
- Interventions
- Drug: APL-2Other: Sham Procedure
- Registration Number
- NCT03525600
- Lead Sponsor
- Apellis Pharmaceuticals, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 621
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description APL-2 15mg 0.1 mL monthly for 24 months APL-2 A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every month APL-2 15mg 0.1 mL EOM for 24 months APL-2 A single dose of 15 mg APL-2/0.1 mL will be administered via intravitreal injection in this study. Subjects will receive an injection every other month Sham Procedure Every Other Month for 24 months Sham Procedure Sham Procedure every other month for 24 months Sham Procedure Monthly for 24 months Sham Procedure Sham Procedure for 24 months
- Primary Outcome Measures
Name Time Method Least Squares (LS) Mean Change From Baseline in Total Area of GA Lesions in the Study Eye at Month 12 Baseline (screening) and 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.
- Secondary Outcome Measures
Name Time Method Mean Change in Total Area of GA Lesions in the Study Eye Through Month 24 From Baseline (screening) 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.
LS Mean Change From Baseline in the Total Area of GA Lesions in the Study Eye at Month 24 Baseline (screening) and 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.
LS Mean Change From Baseline in Mean Functional Reading Independence (FRI) Index Score at Month 24 Baseline (screening) and 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.
LS Mean Change From Baseline in Monocular Maximum Reading Speed of the Study Eye at Month 24 Baseline (screening) and 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.
LS Mean Change From Baseline in Normal-Luminance Best-Corrected Visual Acuity (NL-BCVA) Score of the Study Eye at Month 24 Baseline (screening) and 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.
Trial Locations
- Locations (139)
Long Island Vitreoretinal Consultants
🇺🇸Great Neck, New York, United States
Associated Retinal Consultants PC
🇺🇸Traverse City, Michigan, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
Cumberland Valley Retina Consultants, PC
🇺🇸Hagerstown, Maryland, United States
Mid Atlantic Retina Specialists
🇺🇸Hagerstown, Maryland, United States
Retina Specialists
🇺🇸Towson, Maryland, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Centro Médico Teknon
🇪🇸Barcelona, Spain
Shamir Medical Center
🇮🇱Be'er Ya'aqov, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Oftalmika Eye Hospital
🇵🇱Bydgoszcz, Poland
Centrum Medyczne UNO-MED
🇵🇱Tarnow, Poland
Emanuelli Research and Development Center
🇵🇷Arecibo, Puerto Rico
Klinikum rechts der Isar
🇩🇪München, Germany
Retina Specialist
🇳🇿Auckland, New Zealand
Rambam Medical Center
🇮🇱Haifa, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Klinikum der Stadt Ludwigshafen gGmbH
🇩🇪Ludwigshafen, Germany
Instituto Oftalmologico Gómez-Ulla
🇪🇸Santiago De Compostela, Spain
Rabin Medical Center
🇮🇱Petah tikva, Israel
Jasne Blonia Eye Clinic
🇵🇱Łódź, Poland
Eye Clinic, Acre Mill Outpatients, Huddersfield Royal Infirmary
🇬🇧Huddersfield, West Yorkshire, United Kingdom
St James's University Hospital
🇬🇧Leeds, United Kingdom
Diagnostico Ocular
🇦🇷Buenos Aires, Argentina
University Hospital Würzburg
🇩🇪Würzburg, Germany
Hospital Universitario Rio Hortega
🇪🇸Valladolid, Spain
Centrum Diagnostyki i Mikrochirurgii Oka - LENS
🇵🇱Olsztyn, Poland
University Hospital Cologne
🇩🇪Cologne, Germany
Moorfields Eye Hospital NHS Foundation Trust
🇬🇧London, England, United Kingdom
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Universitätsklinikum Regensburg
🇩🇪Regensburg, Germany
Hamilton Eye Clinic
🇳🇿Hamilton, New Zealand
Ospedale San Raffaele
🇮🇹Milano, Italy
Luigi Sacco Hospital
🇮🇹Milano, Italy
London North West University Hospital Trust
🇬🇧London, United Kingdom
Bristol Eye Hospital
🇬🇧Bristol, United Kingdom
King's College Hospital NHS Trust
🇬🇧London, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Oxford Eye Hospital
🇬🇧Oxford, United Kingdom
Salisbury NHS Foundation Trust
🇬🇧Salisbury, United Kingdom
Sunderland Eye Infirmary
🇬🇧Sunderland, United Kingdom
Retina Associates of Cleveland, Inc
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic, Cole Eye Institute
🇺🇸Cleveland, Ohio, United States
Microcirugia Ocular
🇦🇷Rosario, Corrientes, Argentina
Grupo Laser Vision
🇦🇷Rosario, Santa Fe, Argentina
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Midwest Eye Institute
🇺🇸Indianapolis, Indiana, United States
Retina Institute of California dba Acuity Eye Grp
🇺🇸Arcadia, California, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
The Retina Partners
🇺🇸Encino, California, United States
Retina Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Byers Eye Institute at Standford, Stanford School of Medicine
🇺🇸Palo Alto, California, United States
The Gavin Herbert Eye Institute/UC Irvine
🇺🇸Irvine, California, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
Retina Institute of California Medical Group
🇺🇸Palm Desert, California, United States
Retina Consultants San Diego
🇺🇸Poway, California, United States
New England Retina Associates
🇺🇸Hamden, Connecticut, United States
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
Danbury Eye Physicians & Surgeons, P.C. - Danbury
🇺🇸Danbury, Connecticut, United States
Retina Group of New England,PC
🇺🇸Waterford, 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
🇺🇸Palm Beach Gardens, Florida, United States
Eye Associates of Pinellas
🇺🇸Pinellas Park, Florida, United States
East Florida Eye Institute
🇺🇸Stuart, Florida, United States
Southern Vitreoretinal Associates
🇺🇸Tallahassee, Florida, United States
Southeast Retina Center, PC
🇺🇸Augusta, Georgia, United States
Georgia Retina
🇺🇸Marietta, Georgia, United States
Sabates Eye Center
🇺🇸Leawood, Kansas, United States
Elman Retina Group, PA
🇺🇸Baltimore, Maryland, United States
New England Retina Consultants, PC
🇺🇸Springfield, Massachusetts, United States
Associated Retinal Consultants, P.C
🇺🇸Grand Rapids, Michigan, United States
Retina Specialists of Michigan / Foundation for Vision
🇺🇸Grand Rapids, Michigan, United States
Retina Consultants of Michigan
🇺🇸Southfield, Michigan, United States
Retina Associates of New Jersey (NJ Retina)
🇺🇸Teaneck, New Jersey, United States
Western Carolina Retinal Associates
🇺🇸Asheville, North Carolina, United States
Charlotte Eye Ear Nose and Throat Associates, PS
🇺🇸Charlotte, North Carolina, United States
Vitreous Retina Macula Consultants of NY
🇺🇸New York, New York, United States
Graystone Eye
🇺🇸Hickory, North Carolina, United States
Retina Associates of Cleveland, Inc.
🇺🇸Youngstown, Ohio, United States
Retina Associates of Cleveland
🇺🇸Cleveland, Ohio, United States
Mid Atlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Southwest Retina Specialists
🇺🇸Amarillo, Texas, United States
Retina Consultants of Houston, PA
🇺🇸Houston, Texas, United States
Valley Retina Institute, PA
🇺🇸McAllen, Texas, United States
Retina Consultants of Houston
🇺🇸The Woodlands, Texas, United States
Retina Associates of Utah, PC
🇺🇸Murray, Utah, United States
The Retina Group of Washington
🇺🇸Fairfax, Virginia, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Virginia Retina Center
🇺🇸Warrenton, Virginia, United States
Vitreoretinal Associates of Washington
🇺🇸Bellevue, Washington, United States
Spokane Eye Clinical Research
🇺🇸Spokane, Washington, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Fundacion Zambrano
🇦🇷Buenos Aires, Capital Federal, Argentina
Centro Oftalmologico Dr Charles
🇦🇷Buenos Aires, Argentina
Centro Privado de Ojos Romagosa SA
🇦🇷Córdoba, Argentina
Instituto Oftalmologico de Cordoba
🇦🇷Córdoba, Argentina
Oftar Mendoza SRL
🇦🇷Mendoza, Argentina
Oftalmologos Especialistas
🇦🇷Rosario, Argentina
Sydney Retina
🇦🇺Sydney, New South Wales, Australia
Centre for Eye Research Australia
🇦🇺East Melbourne, Victoria, Australia
Retina and Eye Consultants
🇦🇺Hurstville, Australia
Clinica Ocular Oftalmologia LTDA
🇧🇷Vitória, Espirito Santo, Brazil
IPEPO - Instituto Da Visao
🇧🇷São Paulo, Vila Clementino, Brazil
Instituto da Visão - Hospital de Olhos Ltda
🇧🇷Belo Horizonte, Brazil
University of Ottawa Eye Institute
🇨🇦Ottawa, Ontario, Canada
UNIFESP - Federal University
🇧🇷São Paulo, Brazil
Ivey Eye Institute
🇨🇦London, Ontario, Canada
Retina Centre of Ottawa
🇨🇦Ottawa, Canada
Fakultní nemocnice Ostrava
🇨🇿Ostrava-Poruba, Czechia
AXON Clinical, S.R.O.
🇨🇿Praha, Czechia
University Hospital Kralovske Vinochrady
🇨🇿Vinohrady, Czechia
Hopital de la Croix-Rousse
🇫🇷Lyon, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Créteil, 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, France
Universitäts-Augenklinik Bonn
🇩🇪Bonn, Germany
DRY AMD Clinic - St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Clinica Oftalmologica Sao Lucas
🇧🇷Osasco, Sao Paulo, Brazil
Hospital De Clinicas De Porto Alegre
🇧🇷Porto Alegre, Brazil
OFTEX Eye Clinic
🇨🇿Pardubice, Czechia
Organizacion Medica de investigacion
🇦🇷Buenos Aires, Argentina
Pinnacle Research Institute
🇺🇸Fort Lauderdale, Florida, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
Retinal Research Institute
🇺🇸Phoenix, Arizona, United States
Associated Retina Consultants, Ltd
🇺🇸Phoenix, Arizona, United States
University of South Florida (USF) Eye Institute
🇺🇸Tampa, Florida, United States
Retina Associates of Florida
🇺🇸Tampa, Florida, United States
Retina Northwest, PC
🇺🇸Portland, Oregon, United States
Eye Health Northwest
🇺🇸Portland, Oregon, United States
Tennessee Retina, PC
🇺🇸Nashville, Tennessee, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Retinal Consultants of San Antonio
🇺🇸San Antonio, Texas, United States
Retina Consultants of Austin (Retina Research Center)
🇺🇸Austin, Texas, United States
Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
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