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]

Amgen

Status and phase: Completed; Phase 3

Conditions: Neovascular (Wet) Age-related Macular Degeneration (AMD)

Treatments: Drug: ABP 938; Drug: Aflibercept

Study type: Interventional

Funder types: Industry

Identifiers

NCT04270747

2019-002503-17 (EudraCT Number)

20170542

Details and patient eligibility

About

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.

Full 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

Enrollment: 576 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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576 participants in 3 patient groups

ABP 938-Treatment Group A

Experimental group

Description:

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.

Treatment:

Drug: ABP 938

Aflibercept-Treatment Group B1

Active Comparator group

Description:

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.

Treatment:

Drug: Aflibercept

ABP 938-Treatment group B2

Active Comparator group

Description:

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

Treatment:

Drug: Aflibercept

Drug: ABP 938