Clinical trial NCT04270747: 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]
Official title: A Randomized, Double-masked, Phase 3 Study of ABP 938 Efficacy and Safety Compared to Aflibercept (Eylea®) in Subjects With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neovascular (Wet) Age-related Macular Degeneration (AMD)
Lead sponsor: Amgen
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2020-02-17
Enrollment: 576
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Mean Change From Baseline in BCVA at Week 8
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Percentage of Participants Who Maintained Vision at Week 52
timeFrame: Week 52
measure: Mean Change From Baseline in BCVA
timeFrame: Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52
measure: Percentage of Participants Who Gained at Least 10 Letters of Vision at Week 8
timeFrame: Week 8
measure: Percentage of Participants Who Gained at Least 15 Letters of Vision at Week 52
timeFrame: Week 52
measure: Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size
timeFrame: Baseline and Weeks 8, 16, 24, and 52
measure: Mean Change From Baseline in Central Subfield Thickness (CST)
timeFrame: Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Week 52
measure: Number of Participants Developing Binding Antidrug Antibodies (ADAs)
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Associated Retina Consultants, Ltd. - Research
state: Arizona
city: Fullerton
country: United States
facility: Retina Consultants of Orange County
state: California
city: La Jolla
country: United States
facility: UCSD Shiley Eye Institute, Jacobs Retina Center
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute, UCLA
state: California
city: Palm Desert
country: United States
facility: Southern California Desert Retina Consultants
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: Sacramento
country: United States
facility: Retinal Consultants Medical Group, Inc.
state: California
city: Santa Ana
country: United States
facility: Orange County Retina Medical Group
state: California
city: Ventura
country: United States
facility: Miramar Eye Specialists
state: California
city: Lakewood
country: United States
facility: Colorado Retina Associates
state: Colorado
city: Waterford
country: United States
facility: Retina Group of New England
state: Connecticut
city: Lakeland
country: United States
facility: Florida Retina Consultants
state: Florida
city: Miami
country: United States
facility: Medeye Associates
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
state: Georgia
city: Marietta
country: United States
facility: Georgia Retina, P.C.
state: Georgia
city: Elmhurst
country: United States
facility: Retina Associates IL
state: Illinois
city: Leawood
country: United States
facility: Sabates Eye Center
state: Kansas
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: Jackson
country: United States
facility: Specialty Eye Institute
state: Michigan
city: Saint Louis Park
country: United States
facility: Retina Center
state: Minnesota
city: Liverpool
country: United States
facility: Retina Vitreous Surgeons of Central NY, PC
state: New York
city: New York
country: United States
facility: Macula Care
state: New York
city: Troy
country: United States
facility: Ophthalmic Consultants of the Capital Region - Ophthalmology
state: New York
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose & Throat Associates, P.A.
state: North Carolina
city: Cincinnati
country: United States
facility: Sterling Research Group
state: Ohio
city: Kingston
country: United States
facility: Eye Care Specialists
state: Pennsylvania
city: Ladson
country: United States
facility: Charleston Neuroscience Institute
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute - Ophthalmology
state: South Dakota
city: Abilene
country: United States
facility: Retina Research Institute of Texas
state: Texas
city: Bellaire
country: United States
facility: Retina Consultants of Texas Research Centers
state: Texas
city: Dallas
country: United States
facility: Texas Retina Associates
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Fort Worth
country: United States
facility: Texas Retina Associates
state: Texas
city: Fort Worth
country: United States
facility: Ophthalmology Associates
state: Texas
city: Midland
country: United States
facility: Premiere Retina Specialists
state: Texas
city: San Antonio
country: United States
facility: Retina Associates of South Texas, P.A.
state: Texas
city: The Woodlands
country: United States
facility: Retina Consultants of Houston
state: Texas
city: Willow Park
country: United States
facility: Strategic Clinical Research
state: Texas
city: Ottawa
country: Canada
facility: University of Ottawa Eye Institute
state: Ontario
city: Boisbriand
country: Canada
facility: Clinique d'ophtalmologie des laurentides
state: Quebec
city: Pardubice
country: Czechia
facility: Ocni klinika Pardubice
city: Praha 10
country: Czechia
facility: FN Kralovske Vinohrady
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 5
country: Czechia
facility: Axon Clinical, s.r.o.
city: Usti nad Labem
country: Czechia
facility: Krajska zdravotni, a.s. Masarykova nemocnice v Usti n/ Labem
state: Ústí Nad Labem
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital - Eye Clinic
state: Harjumaa
city: Tallinn
country: Estonia
facility: Eye Clinic of Dr. Krista Turman
state: Harjumaa
city: Tallinn
country: Estonia
facility: Silmalaser OÜ
state: Harjumaa
city: Tartu
country: Estonia
facility: Eye Clinic of Tartu University Hospital
state: Tartumaa
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
state: Baden-Württemberg
city: Darmstadt
country: Germany
facility: Klinikum Darmstadt
state: Hessen
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
state: Niedersachsen
city: Münster
country: Germany
facility: St. Franziskus Hospital Münster
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin KöR
city: Leipzig
country: Germany
facility: University Hospital Of Leipzig
city: Aberdeen
country: Hong Kong
facility: The University of Hong Kong - Department of Ophthalmology
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital - Department of Ophthalmology and Visual Sciences
city: Pécs
country: Hungary
facility: Ganglion Orvosi Központ
state: Baranya
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo
state: Csongrád
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
state: Hajdú-Bihar
city: Budapest
country: Hungary
facility: Péterfy Kórház-Rendelintézet és Manninger Jen Országos Traumatológiai Intézet - Szemészeti Osztály
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Kórház és Rendelintézet
city: Budapest
country: Hungary
facility: Budapest Retina Intezet
city: Budapest
country: Hungary
facility: MH Egészségügyi Központ
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Be er-Sheva
country: Israel
facility: Soroka University Medical Center
state: HaDarom
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
state: HaDarom
city: Kfar Saba
country: Israel
facility: Meir Medical Center
state: HaMerkaz
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh Medical Center
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata, UNIT Patologie Retiniche
state: Lazio
city: Rome
country: Italy
facility: UOC Oculistica Fondazione PU A.Gemelli IRCCS Un.Cattolica del Sacro Cuore
state: Lazio
city: Perugia
country: Italy
facility: Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia, Clinica Oculistica
state: Umbria
city: Bologna
country: Italy
facility: UO Oftalmologia Ciardella Pol. S.Orsola Malpighi AOU di Bologna
city: Milano
country: Italy
facility: "Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Oculistica Dipartimento di Chirurgia"
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aiti
city: Nagoya
country: Japan
facility: Nagoya City University Hospital - Ophthalmology
state: Aiti
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aiti
city: Asahikawa
country: Japan
facility: Asahikawa Medical University Hospital
state: Hokkaidô
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital - Ophthalmology
state: Hukusima
city: Kagoshima
country: Japan
facility: Kagoshima University Hospital - Ophthalmology
state: Kagosima
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Tokyo
country: Japan
facility: Nihon University Hospital - Ophthalmology
state: Tôkyô
city: Chuo
country: Japan
facility: University of Yamanashi Hospital
state: Yamanasi
city: Akita
country: Japan
facility: Akita University Hospital - Ophthalmology
city: Nagasaki
country: Japan
facility: Nagasaki University Hospital - Ophthalmology
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital - Ophthalmology
state: Ôsaka
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - Ophthalmology
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital - Neurology
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital - Department of Ophthalmology
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital - Ophthalmology
city: Riga
country: Latvia
facility: P.Stradina Clinical University Hospital
state: Rga
city: Jelgava
country: Latvia
facility: Signes Ozolinas Doctor Praxis in Ophthalmology
city: Klaipeda
country: Lithuania
facility: Klaipedos Universitetine ligoniene
state: Klaipdos Apskritis
city: Vilnius
country: Lithuania
facility: Vilniaus Universiteto Ligonines Santariskiu Klinikos (VULSK)
state: Vilniaus Apskritis
city: Gdansk
country: Poland
facility: Profesorskie Centrum Okulistyki OKULISTYKA OPTIMUM
state: Pomorskie
city: Poznan
country: Poland
facility: Szpital Sw. Wojciecha
state: Wielkopolskie
city: Krakow
country: Poland
facility: Centrum Medyczne PROMED
city: Olsztyn
country: Poland
facility: Centrum Diagnostyki i Mikrochirurgii Oka-Lens Sp. z o.o.
city: Tarnow
country: Poland
facility: Centrum Medyczne UNO-MED
city: Lodz
country: Poland
facility: Klinika Okulistyczna "Jasne Blonia"
state: Ódzkie
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava
state: Bratislavský Kraj
city: Zilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou Zilina
state: Ilinský Kraj
city: Trencin
country: Slovakia
facility: Fakultna nemocnica Trencin
state: Treniansky Kraj
city: LHospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: FISABIO - Oftalmología Médica
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: