A Study to Understand Effectiveness and Safety of ABP 938 Compared to Aflibercept (Eylea®) in Patients Suffering With Neovascular Age-related Macular Degeneration [Neovascular (Wet) AMD]
- Conditions
- Neovascular (Wet) Age-related Macular Degeneration (AMD)
- Interventions
- Registration Number
- NCT04270747
- Lead Sponsor
- Amgen
- Brief Summary
The purpose of this study is to compare the efficacy and safety of ABP 938 versus Aflibercept (Eylea®) in the treatment of neovascular age-related macular degeneration. Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by intravitreal (IVT) injection.
- Detailed Description
Approximately 566 subjects will be randomized in approximately 126 global sites.
This study consists of a screening period of up to 4 weeks, after which subjects will receive investigational product for 48 weeks, followed by a safety follow-up period to week 52, for a total study duration of up to 56 weeks.
Subjects will be randomized in a masked 1:1 ratio to receive 2 mg (0.05 mL) of either ABP 938 (Treatment Group A) or aflibercept (Treatment Group B) administered by IVT injection.
At week 8, subjects will be assessed for the primary endpoint. The primary endpoint is the change in Best Corrected Visual Acuity (BCVA) as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline to week 8, in order to assess the efficacy of ABP 938 compared to aflibercept.
Subjects will then be re-randomized at week 16 in a masked fashion such that:
* Subjects initially randomized to ABP 938 (Treatment Group A) will continue to receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48
* Subjects initially randomized to aflibercept (Treatment Group B) will be re-randomized in a 1:1 ratio to either continue on aflibercept (Treatment Group B1) or transition to ABP 938 (Treatment Group B2) by IVT injection every 8 weeks from week 16 until week 48
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 576
- Subjects or their legally authorized representative must sign an Institutional Review Board/Independent Ethics Committee approved informed consent form before any study-specific procedures
- Men or women ≥ 50 years old
- Subjects must be diagnosed with neovascular (wet) AMD in the study eye
- Active treatment naïve subfoveal CNV lesions secondary to neovascular (wet) AMD including juxtafoveal lesions that affect the fovea as confirmed with SD OCT, FA and/or Fundus Photography (FP) in the study eye
- BCVA between 73 and 34 letters, inclusive, in the study eye using ETDRS testing
- Presence of intra and/or subretinal fluid as identified by SD-OCT attributable to active CNV in the study eye
- Central retinal thickness of > 270µm in the study eye as measured by the machine, calculated average thickness in the central 1 mm subfield (CST) by SD-OCT at screening
Subjects are excluded if they meet any of the following criteria in the study eye:
- Total lesion size > 12 disc areas (30.5 mm^2, including blood, scars, and neovascularization) in the study eye
- Active CNV area (classic plus occult components) that is < 50% of the total lesion area in the study eye
- Scar, fibrosis, or atrophy involving the center of the fovea in the study eye
- Presence of retinal pigment epithelium tears or rips involving the macula in the study eye
- History of any vitreous hemorrhage within 4 weeks before randomization in the study eye
- Presence of other causes of CNV, including pathologic myopia (spherical equivalent of 8 diopters or more negative or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye
- Prior vitrectomy or laser surgery of the macula (including photodynamic therapy or focal laser photocoagulation) in the study eye
- History of retinal detachment in the study eye
- Any history of macular hole of stage 2 and above in the study eye
- Any macular pathology that might limit vision i.e., Vitreomacular traction or significant epiretinal membrane in the study eye
- Any intraocular or periocular surgery within 3 months before randomization on the study eye, except lid surgery, which may not have taken place within 4 weeks before randomization, as long as it is unlikely to interfere with the injection
- Prior trabeculectomy or other filtration surgery in the study eye
- Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye
- Aphakia or pseudophakia with complete absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye
- Previous therapeutic radiation in the region of the study eye
- History of corneal transplant or corneal dystrophy in the study eye
- Significant media opacities, including cataract, which might interfere with visual acuity or assessment of safety, in the study eye
- Any concurrent intraocular condition other than neovascular (wet) AMD in the study eye that, in the opinion of the investigator, requires planned medical or surgical intervention during the study or increases the risk to the subject beyond what is expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety
Subjects are excluded if they meet any of the following criteria in either eye:
- History or clinical evidence of uveitis, diabetic retinopathy, diabetic macular edema, or any other vascular disease affecting the retina, other than neovascular (wet) AMD
- Active intraocular inflammation or active or suspected ocular or periocular infection, within 2 weeks before randomization
- Active scleritis or episcleritis or presence of scleromalacia
Other Medical Conditions
• Active extraocular infection or history of extraocular infections as follows: A. any active infection for which systemic anti-infectives were used within 4 weeks before randomization B. recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject
- Acute coronary event or stroke within 3 months before randomization
- Uncontrolled, clinically significant systemic disease such as diabetes mellitus, hypertension, cardiovascular disease including moderate to severe heart failure (New York Heart Association class III/IV), renal disease, or liver disease
- Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma
Washouts and Nonpermitted Treatments
- Any prior ocular or systemic treatment, including another investigational product or surgery for neovascular (wet) AMD (including anti vascular endothelial growth factor [VEGF] therapy) in the study eye, except dietary supplements or vitamins
- Any ocular or systemic treatment including another investigational product or surgery for neovascular (wet) AMD (including anti VEGF therapy) in the fellow eye, within 30 days before randomization, except dietary supplements or vitamins
- Prior systemic anti-VEGF treatment as follows:
- Investigational or approved anti-VEGF therapy systemically within 3 months before randomization
- Aflibercept, ziv-aflibercept, or a biosimilar of aflibercept/ziv-aflibercept systemically at any time
- Any IVT therapy, including adrenocorticotropic hormone, in the study or fellow eye, or intramuscular or intravenous corticosteroids within 4 weeks before randomization. The use of long-acting steroids, either systemically or intraocularly, in the 3 months before randomization
- Currently receiving treatment with another investigational device or study drug, or less than 30 days or 5 half-lives (whichever is longer) since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded
General
- For women: pregnant or breast feeding, or planning to become pregnant while enrolled in the study and for 3 months after the last dose of investigational product
- Sexually active subjects and their partners who are of childbearing potential (ie, neither surgically sterile nor postmenopausal) and not agreeing to use adequate contraception (eg, true abstinence, sterilization, birth control pills, Depo Provera injections, contraceptive implants, or other effective methods) while on study and for 3 months after the last dose of study drug. Male subjects must agree not to donate sperm during study and for 3 months following treatment with test article or until the scheduled end of the study (whichever is longer)
- Allergy or hypersensitivity to investigational product, to any of the excipients of ABP 938 or aflibercept, or to other study-related procedures/medications (eg, anesthesia, antiseptic, fluorescein dye)
- History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ABP 938-Treatment Group A ABP 938 Subjects will receive 2 mg (0.05 mL) of ABP 938 by intravitreal (IVT) injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8) and every 8 weeks from week 16 until week 48. ABP 938-Treatment group B2 ABP 938 Subjects will receive 2 mg (0.05 mL) of aflibercept (Treatment Group B) by IVT injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8). Subjects will be re-randomized to receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48 Aflibercept-Treatment Group B1 Aflibercept Subjects will receive 2 mg (0.05 mL) of aflibercept (Treatment Group B) by IVT injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8). Subjects will be re-randomized to receive aflibercept by IVT injection every 8 weeks from week 16 until week 48. ABP 938-Treatment group B2 Aflibercept Subjects will receive 2 mg (0.05 mL) of aflibercept (Treatment Group B) by IVT injection every 4 weeks for the first 3 doses (ie, baseline/day 1, week 4, and week 8). Subjects will be re-randomized to receive ABP 938 by IVT injection every 8 weeks from week 16 until week 48
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in BCVA at Week 8 Baseline and Week 8 BCVA score was assessed based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment.
A positive change from Baseline in ETDRS letter score indicated an improvement in visual acuity in the study eye. Change from Baseline calculated as observed post-baseline value - Baseline value.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in BCVA Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52 BCVA score was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment.
A positive change from Baseline in ETDRS letter score indicated an improvement in visual acuity in the study eye. Change from Baseline calculated as observed post-baseline value - Baseline value.Number of Participants With Treatment-emergent Adverse Events (TEAEs) Up to Week 52 An adverse event (AE) is any untoward medical occurrence in a clinical trial participant. TEAEs were defined as those AEs that begin or increase in severity or frequency at or after the time of first treatment to the End of Study visit. Events of interest (EOIs) pre-specified for this study included endophthalmitis, retinal detachment, increase in intraocular pressure, and thromboembolic events. Serious AEs were defined as any untoward medical occurrence that meets at least 1 of the following serious criteria:
* Results in death
* Life-threatening
* Requires inpatient hospitalization or prolongation of existing hospitalization
* Results in persistent or significant disability/incapacity
* Congenital anomaly/birth defect
* Other medically important serious event.Percentage of Participants Who Maintained Vision at Week 52 Week 52 A participant was classified as maintaining vision if he/she lost fewer than 15 letters in ETDRS letter score, assessed in the study eye, compared to Baseline.
Percentage of Participants Who Gained at Least 10 Letters of Vision at Week 8 Week 8 Percentage of participants who gained at least 10 letters of vision was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment.
Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52 Week 52 Percentage of participants who gained at least 15 letters of vision was assessed based on the number of letters read correctly on the ETDRS chart by the study eye at 4 meters. ETDRS letters score could range from 0 to 100 letters at each assessment.
Number of Participants Developing Binding Antidrug Antibodies (ADAs) Baseline up to Week 52 Number of participants with positive post-baseline ADA result through Week 16 and post Week 16 with negative or no result at Baseline is reported.
Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size Baseline and Weeks 8, 16, 24, and 52 CNV area size was measured by fluorescein angiography.
Change from Baseline calculated as observed post-baseline value - Baseline value.Mean Change From Baseline in Central Subfield Thickness (CST) Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52 CST was defined as the average thickness in the ETDRS central 1 mm diameter subfield (the central subfield) and was measured by spectral domain optical coherence tomography.
Change from Baseline calculated as observed post-baseline value - Baseline value.
Trial Locations
- Locations (115)
Clinique d'ophtalmologie des laurentides
🇨🇦Boisbriand, Quebec, Canada
Szpital Sw. Wojciecha
🇵🇱Poznan, Wielkopolskie, Poland
Univerzitna nemocnica Bratislava
🇸🇰Bratislava, Bratislavský Kraj, Slovakia
"Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Oculistica Dipartimento di Chirurgia"
🇮🇹Milano, Italy
Florida Retina Consultants
🇺🇸Lakeland, Florida, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
Jules Stein Eye Institute, UCLA
🇺🇸Los Angeles, California, United States
University of Ottawa Eye Institute
🇨🇦Ottawa, Ontario, Canada
Miramar Eye Specialists
🇺🇸Ventura, California, United States
Retina Consultants of Southern California
🇺🇸Redlands, California, United States
Retina Consultants San Diego
🇺🇸Poway, California, United States
Colorado Retina Associates
🇺🇸Lakewood, Colorado, United States
Charleston Neuroscience Institute
🇺🇸Ladson, South Carolina, United States
Retina Associates IL
🇺🇸Elmhurst, Illinois, United States
Retina Research Institute of Texas
🇺🇸Abilene, Texas, United States
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Georgia Retina, P.C.
🇺🇸Marietta, Georgia, United States
The Retina Care Center
🇺🇸Baltimore, Maryland, United States
Retina Vitreous Surgeons of Central NY, PC
🇺🇸Liverpool, New York, United States
Black Hills Regional Eye Institute - Ophthalmology
🇺🇸Rapid City, South Dakota, United States
MH Egészségügyi Központ
🇭🇺Budapest, Hungary
FN Kralovske Vinohrady
🇨🇿Praha 10, Czechia
Axon Clinical, s.r.o.
🇨🇿Praha 5, Czechia
Charlotte Eye Ear Nose & Throat Associates, P.A.
🇺🇸Charlotte, North Carolina, United States
Ocni klinika Pardubice
🇨🇿Pardubice, Czechia
Texas Retina Associates
🇺🇸Fort Worth, Texas, United States
Bajcsy-Zsilinszky Kórház és Rendelintézet
🇭🇺Budapest, Hungary
Silmalaser OÜ
🇪🇪Tallinn, Harjumaa, Estonia
Eye Clinic of Tartu University Hospital
🇪🇪Tartu, Tartumaa, Estonia
Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia, Clinica Oculistica
🇮🇹Perugia, Umbria, Italy
Meir Medical Center
🇮🇱Kfar Saba, HaMerkaz, Israel
Mie University Hospital
🇯🇵Tsu, Mie, Japan
University Medical Center Freiburg
🇩🇪Freiburg, Baden-Württemberg, Germany
Prince of Wales Hospital - Department of Ophthalmology and Visual Sciences
🇭🇰Shatin, New Territories, Hong Kong
Debreceni Egyetem Klinikai Központ
🇭🇺Debrecen, Hajdú-Bihar, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
🇭🇺Szeged, Csongrád, Hungary
Klinikum Darmstadt
🇩🇪Darmstadt, Hessen, Germany
Budapest Retina Intezet
🇭🇺Budapest, Hungary
St. Franziskus Hospital Münster
🇩🇪Münster, Nordrhein-Westfalen, Germany
Ganglion Orvosi Központ
🇭🇺Pécs, Baranya, Hungary
University Hospital Of Leipzig
🇩🇪Leipzig, Germany
Péterfy Kórház-Rendelintézet és Manninger Jen Országos Traumatológiai Intézet - Szemészeti Osztály
🇭🇺Budapest, Hungary
Soroka University Medical Center
🇮🇱Be er-Sheva, HaDarom, Israel
Bnai Zion Medical Center
🇮🇱Haifa, HaDarom, Israel
Fondazione PTV Policlinico Tor Vergata, UNIT Patologie Retiniche
🇮🇹Roma, Lazio, Italy
Fukushima Medical University Hospital - Ophthalmology
🇯🇵Fukushima, Hukusima, Japan
Korea University Anam Hospital - Ophthalmology
🇰🇷Seoul, Korea, Republic of
Kaplan Medical Center
🇮🇱Rehovot, Israel
Nagoya University Hospital
🇯🇵Nagoya, Aiti, Japan
Nihon University Hospital - Ophthalmology
🇯🇵Tokyo, Tôkyô, Japan
Akita University Hospital - Ophthalmology
🇯🇵Akita, Japan
Nagasaki University Hospital - Ophthalmology
🇯🇵Nagasaki, Japan
UO Oftalmologia Ciardella Pol. S.Orsola Malpighi AOU di Bologna
🇮🇹Bologna, Italy
Assaf Harofeh Medical Center
🇮🇱Zerifin, Israel
UOC Oculistica Fondazione PU A.Gemelli IRCCS Un.Cattolica del Sacro Cuore
🇮🇹Rome, Lazio, Italy
Nagoya City University Hospital - Ophthalmology
🇯🇵Nagoya, Aiti, Japan
Asahikawa Medical University Hospital
🇯🇵Asahikawa, Hokkaidô, Japan
Kagoshima University Hospital - Ophthalmology
🇯🇵Kagoshima, Kagosima, Japan
Asan Medical Center
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
P.Stradina Clinical University Hospital
🇱🇻Riga, Rga, Latvia
Signes Ozolinas Doctor Praxis in Ophthalmology
🇱🇻Jelgava, Latvia
Vilniaus Universiteto Ligonines Santariskiu Klinikos (VULSK)
🇱🇹Vilnius, Vilniaus Apskritis, Lithuania
Profesorskie Centrum Okulistyki OKULISTYKA OPTIMUM
🇵🇱Gdansk, Pomorskie, Poland
Samsung Medical Center - Ophthalmology
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Centro Medico Zambrano Hellion
🇲🇽Monterrey, Nuevo León, Mexico
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Klaipedos Universitetine ligoniene
🇱🇹Klaipeda, Klaipdos Apskritis, Lithuania
Asociación para Evitar la Ceguera en México I.A.P.
🇲🇽México DF, Distrito Federal, Mexico
Centrum Medyczne UNO-MED
🇵🇱Tarnow, Poland
Hospital Universitario Reina Sofía
🇪🇸Córdoba, Spain
Centro de Retina Medica y Quirurgica S.C.
🇲🇽Zapopan, Mexico
Centrum Medyczne PROMED
🇵🇱Krakow, Poland
Klinika Okulistyczna "Jasne Blonia"
🇵🇱Lodz, Ódzkie, Poland
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Fakultna nemocnica s poliklinikou Zilina
🇸🇰Zilina, Ilinský Kraj, Slovakia
FISABIO - Oftalmología Médica
🇪🇸Valencia, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
The Catholic University of Korea, Seoul St. Mary's Hospital - Neurology
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital - Department of Ophthalmology
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Universitätsmedizin Göttingen
🇩🇪Göttingen, Niedersachsen, Germany
Retina Center
🇺🇸Saint Louis Park, Minnesota, United States
Orange County Retina Medical Group
🇺🇸Santa Ana, California, United States
Southeast Retina Center
🇺🇸Augusta, Georgia, United States
Macula Care
🇺🇸New York, New York, United States
Ophthalmic Consultants of the Capital Region - Ophthalmology
🇺🇸Troy, New York, United States
Eye Care Specialists
🇺🇸Kingston, Pennsylvania, United States
Retina Consultants of Texas Research Centers
🇺🇸Bellaire, Texas, United States
Ophthalmology Associates
🇺🇸Fort Worth, Texas, United States
Retina Consultants of Houston
🇺🇸The Woodlands, Texas, United States
Associated Retina Consultants, Ltd. - Research
🇺🇸Phoenix, Arizona, United States
Retinal Consultants Medical Group, Inc.
🇺🇸Sacramento, California, United States
Medeye Associates
🇺🇸Miami, Florida, United States
Sterling Research Group
🇺🇸Cincinnati, Ohio, United States
Retina Associates of South Texas, P.A.
🇺🇸San Antonio, Texas, United States
Strategic Clinical Research
🇺🇸Willow Park, Texas, United States
Center for Retina and Macular Disease
🇺🇸Winter Haven, Florida, United States
Charité Universitätsmedizin Berlin KöR
🇩🇪Berlin, Germany
Universitätsmedizin Mainz
🇩🇪Mainz, Rheinland-Pfalz, Germany
Premiere Retina Specialists
🇺🇸Midland, Texas, United States
Southern California Desert Retina Consultants
🇺🇸Palm Desert, California, United States
Retina Group of New England
🇺🇸Waterford, Connecticut, United States
Krajska zdravotni, a.s. Masarykova nemocnice v Usti n/ Labem
🇨🇿Usti nad Labem, Ústí Nad Labem, Czechia
Hospital Universitario de Bellvitge
🇪🇸LHospitalet de Llobregat, Barcelona, Spain
University of Yamanashi Hospital
🇯🇵Chuo, Yamanasi, Japan
Kansai Medical University Hospital - Ophthalmology
🇯🇵Hirakata, Ôsaka, Japan
Centrum Diagnostyki i Mikrochirurgii Oka-Lens Sp. z o.o.
🇵🇱Olsztyn, Poland
Fakultna nemocnica Trencin
🇸🇰Trencin, Treniansky Kraj, Slovakia
Retina Associates New Orleans
🇺🇸Metairie, Louisiana, United States
Semmelweis Egyetem
🇭🇺Budapest, Hungary
East Tallinn Central Hospital - Eye Clinic
🇪🇪Tallinn, Harjumaa, Estonia
Eye Clinic of Dr. Krista Turman
🇪🇪Tallinn, Harjumaa, Estonia
Specialty Eye Institute
🇺🇸Jackson, Michigan, United States
UCSD Shiley Eye Institute, Jacobs Retina Center
🇺🇸La Jolla, California, United States
Sabates Eye Center
🇺🇸Leawood, Kansas, United States
The University of Hong Kong - Department of Ophthalmology
🇭🇰Aberdeen, Hong Kong