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]

Neovascular (Wet) Age-related Macular Degeneration (AMD) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04270747
• Other study ID #: 20170542
• Secondary ID: 2019-002503-17
• Status: Completed
• Phase: Phase 3
• Start date: June 22, 2020
• Est. completion date: January 30, 2023

Study information

• Verified date: November 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 576
• Est. completion date: January 30, 2023
• Est. primary completion date: July 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular (Wet) Age-related Macular Degeneration (AMD)

Intervention

Drug:
• ABP 938
Subject will receive ABP 938 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks
• Aflibercept
Subject will receive aflibercept 2 mg (0.05 mL) IVT injection every 4 weeks for the first 3 doses, followed by once every 8 weeks

Locations

Country	Name	City	State
Canada	Clinique d'ophtalmologie des laurentides	Boisbriand	Quebec
Canada	University of Ottawa Eye Institute	Ottawa	Ontario
Czechia	Ocni klinika Pardubice	Pardubice
Czechia	FN Kralovske Vinohrady	Praha 10
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Czechia	Axon Clinical, s.r.o.	Praha 5
Czechia	Krajska zdravotni, a.s. Masarykova nemocnice v Usti n/ Labem	Usti nad Labem	Ústí Nad Labem
Estonia	East Tallinn Central Hospital - Eye Clinic	Tallinn	Harjumaa
Estonia	Eye Clinic of Dr. Krista Turman	Tallinn	Harjumaa
Estonia	Silmalaser OÜ	Tallinn	Harjumaa
Estonia	Eye Clinic of Tartu University Hospital	Tartu	Tartumaa
Germany	Charité Universitätsmedizin Berlin KöR	Berlin
Germany	Klinikum Darmstadt	Darmstadt	Hessen
Germany	University Medical Center Freiburg	Freiburg	Baden-Württemberg
Germany	Universitätsmedizin Göttingen	Göttingen	Niedersachsen
Germany	University Hospital Of Leipzig	Leipzig
Germany	Universitätsmedizin Mainz	Mainz	Rheinland-Pfalz
Germany	St. Franziskus Hospital Münster	Münster	Nordrhein-Westfalen
Hong Kong	The University of Hong Kong - Department of Ophthalmology	Aberdeen
Hong Kong	Prince of Wales Hospital - Department of Ophthalmology and Visual Sciences	Shatin, New Territories
Hungary	Bajcsy-Zsilinszky Kórház és Rendelintézet	Budapest
Hungary	Budapest Retina Intezet	Budapest
Hungary	MH Egészségügyi Központ	Budapest
Hungary	Péterfy Kórház-Rendelintézet és Manninger Jen Országos Traumatológiai Intézet - Szemészeti Osztály	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem Klinikai Központ	Debrecen	Hajdú-Bihar
Hungary	Ganglion Orvosi Központ	Pécs	Baranya
Hungary	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpo	Szeged	Csongrád
Israel	Soroka University Medical Center	Be er-Sheva	HaDarom
Israel	Bnai Zion Medical Center	Haifa	HaDarom
Israel	Meir Medical Center	Kfar Saba	HaMerkaz
Israel	Kaplan Medical Center	Rehovot
Israel	Assaf Harofeh Medical Center	Zerifin
Italy	UO Oftalmologia Ciardella Pol. S.Orsola Malpighi AOU di Bologna	Bologna
Italy	"Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, UO Oculistica Dipartimento di Chirurgia"	Milano
Italy	Università degli Studi di Perugia, Ospedale Santa Maria della Misericordia, Clinica Oculistica	Perugia	Umbria
Italy	Fondazione PTV Policlinico Tor Vergata, UNIT Patologie Retiniche	Roma	Lazio
Italy	UOC Oculistica Fondazione PU A.Gemelli IRCCS Un.Cattolica del Sacro Cuore	Rome	Lazio
Japan	Akita University Hospital - Ophthalmology	Akita
Japan	Asahikawa Medical University Hospital	Asahikawa	Hokkaidô
Japan	University of Yamanashi Hospital	Chuo	Yamanasi
Japan	Fukushima Medical University Hospital - Ophthalmology	Fukushima	Hukusima
Japan	Kansai Medical University Hospital - Ophthalmology	Hirakata	Ôsaka
Japan	Kagoshima University Hospital - Ophthalmology	Kagoshima	Kagosima
Japan	Nagasaki University Hospital - Ophthalmology	Nagasaki
Japan	Nagoya City University Hospital - Ophthalmology	Nagoya	Aiti
Japan	Nagoya University Hospital	Nagoya	Aiti
Japan	Nagoya University Hospital	Nagoya	Aiti
Japan	Nihon University Hospital - Ophthalmology	Tokyo	Tôkyô
Japan	Mie University Hospital	Tsu	Mie
Korea, Republic of	Asan Medical Center	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Korea University Anam Hospital - Ophthalmology	Seoul
Korea, Republic of	Samsung Medical Center - Ophthalmology	Seoul	Seoul Teugbyeolsi
Korea, Republic of	Seoul National University Hospital - Department of Ophthalmology	Seoul	Seoul Teugbyeolsi
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital - Neurology	Seoul	Seoul Teugbyeolsi
Latvia	Signes Ozolinas Doctor Praxis in Ophthalmology	Jelgava
Latvia	P.Stradina Clinical University Hospital	Riga	Rga
Lithuania	Klaipedos Universitetine ligoniene	Klaipeda	Klaipdos Apskritis
Lithuania	Vilniaus Universiteto Ligonines Santariskiu Klinikos (VULSK)	Vilnius	Vilniaus Apskritis
Mexico	Asociación para Evitar la Ceguera en México I.A.P.	México DF	Distrito Federal
Mexico	Centro Medico Zambrano Hellion	Monterrey	Nuevo León
Mexico	Centro de Retina Medica y Quirurgica S.C.	Zapopan
Poland	Profesorskie Centrum Okulistyki OKULISTYKA OPTIMUM	Gdansk	Pomorskie
Poland	Centrum Medyczne PROMED	Krakow
Poland	Klinika Okulistyczna "Jasne Blonia"	Lodz	Ódzkie
Poland	Centrum Diagnostyki i Mikrochirurgii Oka-Lens Sp. z o.o.	Olsztyn
Poland	Szpital Sw. Wojciecha	Poznan	Wielkopolskie
Poland	Centrum Medyczne UNO-MED	Tarnow
Serbia	Clinical Center of Serbia	Belgrade
Slovakia	Univerzitna nemocnica Bratislava	Bratislava	Bratislavský Kraj
Slovakia	Fakultna nemocnica Trencin	Trencin	Treniansky Kraj
Slovakia	Fakultna nemocnica s poliklinikou Zilina	Zilina	Ilinský Kraj
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario de Bellvitge	LHospitalet de Llobregat	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	FISABIO - Oftalmología Médica	Valencia
United States	Retina Research Institute of Texas	Abilene	Texas
United States	Southeast Retina Center	Augusta	Georgia
United States	The Retina Care Center	Baltimore	Maryland
United States	Retina Consultants of Texas Research Centers	Bellaire	Texas
United States	Charlotte Eye Ear Nose & Throat Associates, P.A.	Charlotte	North Carolina
United States	Sterling Research Group	Cincinnati	Ohio
United States	Texas Retina Associates	Dallas	Texas
United States	Retina Associates IL	Elmhurst	Illinois
United States	Ophthalmology Associates	Fort Worth	Texas
United States	Texas Retina Associates	Fort Worth	Texas
United States	Texas Retina Associates	Fort Worth	Texas
United States	Retina Consultants of Orange County	Fullerton	California
United States	Specialty Eye Institute	Jackson	Michigan
United States	Eye Care Specialists	Kingston	Pennsylvania
United States	UCSD Shiley Eye Institute, Jacobs Retina Center	La Jolla	California
United States	Charleston Neuroscience Institute	Ladson	South Carolina
United States	Florida Retina Consultants	Lakeland	Florida
United States	Colorado Retina Associates	Lakewood	Colorado
United States	Sabates Eye Center	Leawood	Kansas
United States	Retina Vitreous Surgeons of Central NY, PC	Liverpool	New York
United States	Jules Stein Eye Institute, UCLA	Los Angeles	California
United States	Georgia Retina, P.C.	Marietta	Georgia
United States	Retina Associates New Orleans	Metairie	Louisiana
United States	Medeye Associates	Miami	Florida
United States	Premiere Retina Specialists	Midland	Texas
United States	Macula Care	New York	New York
United States	Southern California Desert Retina Consultants	Palm Desert	California
United States	Associated Retina Consultants, Ltd. - Research	Phoenix	Arizona
United States	Retina Consultants San Diego	Poway	California
United States	Black Hills Regional Eye Institute - Ophthalmology	Rapid City	South Dakota
United States	Retina Consultants of Southern California	Redlands	California
United States	Retinal Consultants Medical Group, Inc.	Sacramento	California
United States	Retina Center	Saint Louis Park	Minnesota
United States	Retina Associates of South Texas, P.A.	San Antonio	Texas
United States	Orange County Retina Medical Group	Santa Ana	California
United States	Retina Consultants of Houston	The Woodlands	Texas
United States	Ophthalmic Consultants of the Capital Region - Ophthalmology	Troy	New York
United States	Miramar Eye Specialists	Ventura	California
United States	Retina Group of New England	Waterford	Connecticut
United States	Strategic Clinical Research	Willow Park	Texas
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Amgen	Parexel

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Estonia,  Germany,  Hong Kong,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Poland,  Serbia,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in BCVA at 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.	Baseline and Week 8
Secondary	Percentage of Participants Who Maintained Vision at 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.	Week 52
Secondary	Mean Change From Baseline in BCVA	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.	Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52
Secondary	Percentage of Participants Who Gained at Least 10 Letters of Vision at 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.	Week 8
Secondary	Percentage of Participants Who Gained at Least 15 Letters of Vision at 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.	Week 52
Secondary	Mean Change From Baseline in Choroidal Neovascularization (CNV) Area Size	CNV area size was measured by fluorescein angiography.; Change from Baseline calculated as observed post-baseline value - Baseline value.	Baseline and Weeks 8, 16, 24, and 52
Secondary	Mean Change From Baseline in Central Subfield Thickness (CST)	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.	Baseline and Weeks 4, 8, 16, 24, 32, 40, 48, and 52
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	Up to Week 52
Secondary	Number of Participants Developing Binding Antidrug Antibodies (ADAs)	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.	Baseline up to Week 52

External Links

•   AmgenTrials clinical trials website