A Phase 3 Safety and Efficacy Study of Intravitreal Administration of Zimura (Complement C5 Inhibitor)
- Conditions
- Geographic AtrophyMacular Degeneration
- Interventions
- Drug: Avacincaptad PegolDrug: Sham
- Registration Number
- NCT04435366
- Lead Sponsor
- IVERIC bio, Inc.
- Brief Summary
The objectives of this study was to evaluate the safety and efficacy of avacincaptad pegol intravitreal administration in participants with geographic atrophy secondary to age-related macular degeneration (AMD)
- Detailed Description
Participants were randomized in a 1:1 ratio to the following monthly treatment groups:
* Avacincaptad pegol 2 mg
* Sham
At Month 12, the participants in the avacincaptad pegol 2mg treatment group were re-randomized to receive the study drug either on a monthly basis or on an every other month basis
The participants initially randomized to sham treatment continued with monthly sham administration through Month 23
All participants had a final follow up visit at Month 24
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 448
- Subjects of either gender aged ≥ 50 years
- Diagnosis of Non-foveal GA secondary to dry AMD
- Any prior treatment for AMD (dry or wet) or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals
- Any intraocular surgery or thermal laser within 3 months of trial entry.
- Any prior thermal laser in the macular region, regardless of indication
- Any ocular or periocular infection (including blepharitis), or ocular surface inflammation in the past 12 weeks.
- Previous therapeutic radiation in the region of the study eye
- Any sign of diabetic retinopathy in either eye
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Avacincaptad Pegol Avacincaptad Pegol Participants received avacincaptad pegol (ACP) 2 milligram (mg)/eye via intravitreal (IVT) injections monthly through Month 11 (Year 1). At month 12, participants were re-randomized to receive ACP 2 mg/eye via IVT injections monthly from month12 through month 23 (Year 2). Sham Sham Participants received sham injections; through Month 11 (Year 1). At month 12, participants continued to receive monthly sham administration from month 12 through month 23 (Year 2). Avacincaptad pegol and Sham Avacincaptad Pegol Participants who received ACP 2mg monthly through Month 11 (Year 1) were re-randomized at month 12, to receive ACP 2 mg/eye via IVT injections every other month at months 13, 15, 17, 19, 21, and 23 and sham injections at months 12, 14, 16,18, 20, and 22.
- Primary Outcome Measures
Name Time Method The Mean Rate of Growth (Slope) Estimated Based on GA Area Measured by Autofluorescence (FAF) at 3 Time Points: Baseline, Month 6, and Month 12 Baseline to month 12 GA was associated with age-related macular degeneration (AMD) and caused bilateral, progressive, and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, and choriocapillaris) leading to a permanent loss of visual function and blindness. The least squares mean used to determine mean rate of change in GA growth (slope) was measured by FAF. LS mean \& SE were based on square-root transformation.
The Mean Rate of Growth (Slope) Estimated Based on GA Area Measured by FAF at 5 Timepoints: Baseline, Month 6, Month 12, Month 18, and Month 24 Baseline to month 24 GA was associated with AMD and caused bilateral, progressive, and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, and choriocapillaris) leading to a permanent loss of visual function and blindness. The least square mean rate of GA growth (slope) was measured by FAF. LS mean \& SE were based on untransformed data.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Best Corrected Visual Acuity (BCVA) Using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 24 Months Baseline and month 24 BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS Visual Acuity Score (VAS) is defined as the number of letters read on the ETDRS chart. Minimum and maximum possible scores are 0-100. A higher score represented better visual functioning. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Change From Baseline in Low Luminance (LL) BCVA Using ETDRS Letters at 24 Months Baseline and month 24 BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS VAS is defined as the number of letters read on the ETDRS chart. Minimum and maximum possible scores are 0-100. A higher score represented better visual functioning. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. LL BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart.
Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Scores at 6, 12 and 18 Months Baseline, months 6, 12, and 18 The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively. Each subscale score had a range of 0 to 100 inclusive and were calculated from the re-scaled raw data. A composite score was derived based on the average of the 11 vision-related subscales.
Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Scores at 24 Months Baseline and month 24 The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively. Each subscale score had a range of 0 to 100 inclusive and were calculated from the re-scaled raw data. A composite score was derived based on the average of the 11 vision-related subscales.
Number of Participants With Categorical One-level Loss in VFQ-25 Subscale Baseline up to month 24 The National Eye Institute VFQ-25 measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively.Categorical one-level loss in each item was defined as decline of one or more levels at Month 24 on the original scale from Baseline (equivalently 20 points for general vision and 25 points for other vision items in a 0 to 100 scale).
Time to Persistent Vision Loss Baseline up to month 24 Vision loss event was defined as a loss of ≥ 15 letters (equivalent to a loss of 3 lines on the ETDRS chart) in BCVA from Baseline measured at any two or more consecutive visits up to Month 24. These parameters were chosen as a 3-line BCVA loss (equivalent to doubling of visual angle) is widely recognized as a significant deterioration in vision and a minimum of two consecutive visits was representative of persistent disease progression. BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS VAS was defined as the number of letters read on the ETDRS chart. Min and max possible scores are 0-100. A higher score represents better visual functioning. Kaplan-Meier method was used for analysis. Participants with an event were reported and not the median time to event.
Trial Locations
- Locations (204)
Jules Stein Eye Institute/David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Retina and Vitreous of Texas, PLLC
🇺🇸Houston, Texas, United States
Cincinnati Eye Institute
🇺🇸Cincinnati, Ohio, United States
Retina Center
🇺🇸Minneapolis, Minnesota, United States
Medical Center Ophthalmology Associates
🇺🇸San Antonio, Texas, United States
Retinal Associates of Utah
🇺🇸Salt Lake City, Utah, United States
Rocky Mountain Retina Consultants
🇺🇸Salt Lake City, Utah, United States
University of Utah, John A. Moran Eye Center
🇺🇸Salt Lake City, Utah, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Retina Consultants of Southern Colorado, P.C.
🇺🇸Colorado Springs, Colorado, United States
Southern California Desert Retina Consultants
🇺🇸Palm Desert, California, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
Rand Eye Institute
🇺🇸Deerfield Beach, Florida, United States
Retina Group of Florida
🇺🇸Fort Lauderdale, Florida, United States
Retina Specialty Institute
🇺🇸Pensacola, Florida, United States
Retina Associates of Sarasota
🇺🇸Sarasota, Florida, United States
Center for Retina and Macula Disease
🇺🇸Winter Haven, Florida, United States
Florida Eye Associates
🇺🇸Melbourne, Florida, United States
University Retina and Macula Associates, PC
🇺🇸Lemont, Illinois, United States
Retina Associates, LLC
🇺🇸Lenexa, Kansas, United States
Retina Consultants of Hawaii, Inc
🇺🇸'Aiea, Hawaii, United States
Georgia Retina, P.C.
🇺🇸Marietta, Georgia, United States
Vitreo Retinal Consultants & Surgeons
🇺🇸Wichita, Kansas, United States
Wolfe Eye Clinic
🇺🇸West Des Moines, Iowa, United States
Sierra Eye Associates
🇺🇸Reno, Nevada, United States
UMASS Memorial Eye Center
🇺🇸Worcester, Massachusetts, United States
Retina Associates of Western NY, PC
🇺🇸Rochester, New York, United States
Western Carolina Retinal Associates
🇺🇸Asheville, North Carolina, United States
Scheie Eye Institute, University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Centro Oftalmológico Dr. Charles SA
🇦🇷Buenos Aires, Caba, Argentina
Carolina Macula and Retina
🇺🇸Mount Pleasant, South Carolina, United States
Vistar Eye Center
🇺🇸Roanoke, Virginia, United States
Retina Foundation of the Southwest
🇺🇸Dallas, Texas, United States
Pacific Northwest Retina
🇺🇸Bellevue, Washington, United States
Retina Center of Texas
🇺🇸Southlake, Texas, United States
Buenos Aires Macula S.A.
🇦🇷Buenos Aires, Caba, Argentina
Instituto Oftalmológico de Buenos Aires
🇦🇷Buenos Aires, Argentina
Medizinische Universitaet Graz - Augenklinik
🇦🇹Graz, Austria
Medizinische Universitaet Innsbruck - Universitaetsklinik fuer Augenheilkunde und Optometrie
🇦🇹Innsbruck, Austria
Centro Privado de Oftalmologia - OFTAR Mendoza SRL
🇦🇷Mendoza, Argentina
CHU Brugmann
🇧🇪Brussels, Belgium
UBC/VGH Eye Care Center
🇨🇦Vancouver, British Columbia, Canada
Hospital Sao Paulo - UNIFESP
🇧🇷Vila Clementino, Brazil
IPEPO - Instituto da visão
🇧🇷São Paulo, Brazil
Canadian Centre for Advanced Eye Therapeutics Inc.
🇨🇦Mississauga, Ontario, Canada
Retina Centre of Ottawa
🇨🇦Ottawa, Canada
Clinical hospital Center Osijek
🇭🇷Osijek, Croatia
CHU Bocage
🇫🇷Dijon, France
Centre d'ophtalmologie Rabelais
🇫🇷Lyon, France
Hopital de la Croix Rousse
🇫🇷Lyon, France
Centre St Exupery
🇫🇷Saint-Cyr-sur-Loire, France
Hôpital Lariboisière
🇫🇷Paris, France
Universitätsklinikum Schleswig-Holstein
🇩🇪Lübeck, Germany
University of Bonn
🇩🇪Bonn, Germany
University Eye Hospital, MHH
🇩🇪Hanover, Germany
Augenklinik University Hospital Cologne
🇩🇪Köln, Germany
Clinic Rechts der Isar
🇩🇪Munich, Germany
Hadassah University Hospital
🇮🇱Jerusalem, Israel
Barzilai Medical Center
🇮🇱Ashkelon, Israel
Edith Wolfson Medical Center
🇮🇱Holon, Israel
Ospedali Riuniti di Ancona
🇮🇹Ancona, Italy
Ospedale Luigi Sacco
🇮🇹Milan, Italy
Institut Catala de Retina
🇪🇸Barcelona, Spain
Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Ospedale Maggiore Policlinico Milano
🇮🇹Milan, Italy
Pauls Stradinis Clinical University Hospital
🇱🇻Riga, Latvia
Fondazione GB Bietti IRCCS
🇮🇹Roma, Italy
Clinica de Oftalmologia Barraquer
🇪🇸Barcelona, Spain
Rio Hortega University Hospital
🇪🇸Valladolid, Spain
IMED Servicio Oftalmología
🇪🇸Valencia, Spain
Hospital La Arruzafa
🇪🇸Córdoba, Spain
Instituto Clinico Quirurgico de Oftalmologia
🇪🇸Bilbao, Spain
Instituto Oftalmologico Gomez-Ulla
🇪🇸Santiago De Compostela, Spain
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Retina Northwest, PC
🇺🇸Portland, Oregon, United States
EyeHealth Northwest
🇺🇸Portland, Oregon, United States
Azienda Ospedaliera Universitaria Careggi
🇮🇹Florence, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milan, Italy
AOU Universita degli Studi della Campania Luigi Vanvitelli UOC Oculistica
🇮🇹Naples, Italy
University of Pisa
🇮🇹Pisa, Italy
Fondazione PTV
🇮🇹Roma, Italy
University Health Network
🇨🇦Toronto, Ontario, Canada
Augenzentrum am St. Franziskus-Hospital
🇩🇪Münster, Germany
Colorado Retina Associates
🇺🇸Lakewood, Colorado, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Eye Medical Center of Fresno
🇺🇸Fresno, California, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
California Retina Consultants
🇺🇸Oxnard, California, United States
Orange County Retinal Medical Group
🇺🇸Santa Ana, California, United States
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
Florida Eye Clinic
🇺🇸Altamonte Springs, Florida, United States
Doheny Eye Center, UCLA
🇺🇸Pasadena, California, United States
Southern Vitreoretinal Associates, PL
🇺🇸Tallahassee, Florida, United States
University of Miami-Bascom Palmer Eye Institute
🇺🇸Miami, Florida, United States
Retina Vitreous Associates of Florida
🇺🇸Saint Petersburg, Florida, United States
East Florida Eye Institute
🇺🇸Stuart, Florida, United States
Midwest Eye Institute
🇺🇸Indianapolis, Indiana, United States
The Retina Group of Washington
🇺🇸Chevy Chase, Maryland, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Illinois Eye Center
🇺🇸Peoria, Illinois, United States
Cumberland Valley Retina Consultants
🇺🇸Hagerstown, Maryland, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
Vitreoretinal Associates, PC
🇺🇸Worcester, Massachusetts, United States
St. Louis University
🇺🇸Saint Louis, Missouri, United States
Associated Retinal Consultants, P.C.
🇺🇸Royal Oak, Michigan, United States
Retina Consultants of Nevada
🇺🇸Henderson, Nevada, United States
Retina Vitreous Surgeons of Central New York, PC
🇺🇸Liverpool, New York, United States
Ophthalmic Consultants of the Capital Region
🇺🇸Troy, New York, United States
OCLI
🇺🇸Oceanside, New York, United States
Vitreous Retina Macula Consultants of New York (VRMNY)
🇺🇸New York, New York, United States
Retina Research of Beaufort, LLC
🇺🇸Beaufort, South Carolina, United States
Charleston Neuroscience Institute
🇺🇸Ladson, South Carolina, United States
Palmetto Retina Center
🇺🇸West Columbia, South Carolina, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Southwest Retina Specialists
🇺🇸Amarillo, Texas, United States
Retinal Consultants of Houston
🇺🇸The Woodlands, Texas, United States
Wagner Macular & Retina Center
🇺🇸Norfolk, Virginia, United States
Retina Center NW, PLLC
🇺🇸Silverdale, Washington, United States
Centro de Diagnóstico y Cirugía Ocular "Oftalmólogos Especialistas"
🇦🇷Rosario, Santa Fe, Argentina
Centro Privado de Ojos Romagosa S.A.
🇦🇷Córdoba, Argentina
Sydney Eye Hospital
🇦🇺Sydney, New South Wales, Australia
Instituto Oftalmológico de Córdoba
🇦🇷Córdoba, Argentina
Sydney Retina Clinic and Day Surgery
🇦🇺Sydney, New South Wales, Australia
Medical University of Vienna
🇦🇹Vienna, Austria
Centro Medico Micro Diagnostico y Microcirugla Ocular
🇦🇷Rosario, Argentina
Hanush Hospital
🇦🇹Vienna, Austria
Centro de Ensino e Pesquisa do Instituto da Visao (CEPIV)
🇧🇷Belo Horizonte, Brazil
Fundacion OJlalmologica Nacional - FUNDONAL
🇨🇴Bogotá, Colombia
Clinica De Oftalmologia Sandiego
🇨🇴Medellín, Antioquia, Colombia
Axon Clinical s.r.o.
🇨🇿Prague, Smichov, Czechia
Hopital Intercommunal
🇫🇷Créteil, France
Dr Kai Noor Silmakabinet
🇪🇪Tallin, Estonia
CHU de Bordeaux - Hopital Pellegrin
🇫🇷Bordeaux, France
Centre d'exploration ophtalmologique de l'Odeon
🇫🇷Paris, France
Centre Paradis Monticelli
🇫🇷Marseille, France
CHU de Nantes
🇫🇷Nantes, France
Centre Ophtalmologique d'Imagerie et de Laser
🇫🇷Paris, France
Centre Pole Vision Val d'Ouest
🇫🇷Écully, France
Fondation Alolphe de Rotschild
🇫🇷Paris, France
RWTH Aachen University
🇩🇪Aachen, Germany
University of Göttingen
🇩🇪Göttingen, Germany
Bajcsy Zsilinszky Kórház - Szemészet
🇭🇺Budapest, Hungary
University clinic Leipzig AÖR
🇩🇪Leipzig, Germany
Ludwig-Maximilians-University Munich
🇩🇪Munich, Germany
Universitätsklinikum Münster
🇩🇪Münster, Germany
Universitäts-Augenklinik
🇩🇪Tübingen, Germany
Hungarian Military Hospital Center
🇭🇺Budapest, Hungary
Semmelweis University, Dept of Ophthalmology
🇭🇺Budapest, Hungary
Debrecen University Clinical Center, Dept of Ophthalmology
🇭🇺Debrecen, Hungary
Szabolcs-Szatmar-Bereg County Hospital and University Teaching Hospital
🇭🇺Nyiregyhaza, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Shamir Medical Center
🇮🇱Be'er Ya'aqov, Israel
Rambam Medical Centre
🇮🇱Haifa, Israel
Carmel Medical Center
🇮🇱Haifa, Israel
Department of Ophthalmology, Rabin Medical Center
🇮🇱Petah tikva, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Nuovo Arcispedale Sant' Anna (A.O.U. di Ferrara)
🇮🇹Ferrara, Italy
A.O.U. Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Ospedale Clinicizzato Universita di Chieti "Ss Annunziata"
🇮🇹Chieti, Italy
Azienda Ospedaliera di Padova Unità Operativa Complessa di Clinica Oculistica
🇮🇹Padova, Italy
Azienda Sanitaria Universitaria Integrata
🇮🇹Udine, Italy
Medical Center Julianów
🇵🇱Łódź, Poland
Institut de la Macula
🇪🇸Barcelona, Spain
VOR - Hospital General de Catalunya
🇪🇸Barcelona, Spain
H.U. Puerta de Hierro-Majadahonda
🇪🇸Majadahonda, Spain
Hospital Clínico Universitario "Lozano Blesa"
🇪🇸Zaragoza, Spain
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Retina Group of New England, PC
🇺🇸Waterford, Connecticut, United States
Retina Care Specialists
🇺🇸Palm Beach Gardens, Florida, United States
Retinal Diagnostic Center
🇺🇸Campbell, California, United States
Connecticut Eye Consultants, P.C.
🇺🇸Danbury, Connecticut, United States
National Ophthalmic Research Institute
🇺🇸Fort Myers, Florida, United States
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
🇩🇪Mainz, Germany
Retina Research Institute at New England Retinal Consultants
🇺🇸Springfield, Massachusetts, United States
Retina Center of New Jersey, LLC
🇺🇸Bloomfield, New Jersey, United States
Long Island Vitreoretinal Consultant
🇺🇸Great Neck, New York, United States
Retina and Vitreous Center of Southern Oregon
🇺🇸Ashland, Oregon, United States
Black Hills Regional Eye Institute
🇺🇸Rapid City, South Dakota, United States
Mid Atlantic Retina
🇺🇸Philadelphia, Pennsylvania, United States
Associates in Ophthalmology, Ltd
🇺🇸West Mifflin, Pennsylvania, United States
Southeastern Retina Associates, PC
🇺🇸Knoxville, Tennessee, United States
Universitätsklinikum Hamburg Eppendorf Klinik und Poliklinik für Augenheilkunde Studienzentrum
🇩🇪Hamburg, Germany
Valley Retina Institute
🇺🇸McAllen, Texas, United States
Strategic Clinical Research Group
🇺🇸Willow Park, Texas, United States
Royal Victorian Eye & Ear Hospital
🇦🇺East Melbourne, Australia
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Calgary Retina Consultants
🇨🇦Calgary, Alberta, Canada
Retina Health Center
🇺🇸Fort Myers, Florida, United States
Ganglion Medical Center
🇭🇺Pécs, Hungary
Caminomed
🇵🇱Tarnowskie Góry, Poland
Klinika Okulistyczna OFT ALMIKA Sp. z o. o.
🇵🇱Bydgoszcz, Poland
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
🇵🇱Wrocław, Poland
Tartu University Hospital
🇪🇪Tartu, Estonia
Budapest Retina Associates
🇭🇺Budapest, Hungary
Retinal Consultants Medical Group, Inc.
🇺🇸Sacramento, California, United States
VitreoRetinal Associates, P.A.
🇺🇸Gainesville, Florida, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Austin Retina Associates
🇺🇸Austin, Texas, United States
Retina Institute of Virginia
🇺🇸Richmond, Virginia, United States
St.Joseph's Health Care London
🇨🇦London, Ontario, Canada
University of Ottawa Eye Institute
🇨🇦Ottawa, Ontario, Canada
Centro Médico Grupo Laser Visión
🇦🇷Rosario, Santa Fe, Argentina
Hull University Teaching Hospitals NHS Trust
🇬🇧Hull, United Kingdom
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