Resumen

This study will evaluate the effectiveness and safety of a 36-week refill regimen for the Port Delivery System with ranibizumab 100 mg/mL (PDS Q36W) compared with intravitreal injections of aflibercept (2 mg) administered per treat-and-extend (aflibercept T\&E) in subjects with neovascular (wet) age-related macular degeneration (nAMD).

Elegibilidad

Edad mínima: 50 YearsSexo: ALL

Criterios de inclusión

Signed Informed Consent Form
Age ≥ 50 years, at time of signing Informed Consent Form
Ability and willingness to undertake all scheduled visits and assessments
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
Initial diagnosis of nAMD within 9 months prior to the screening visit
Previous treatment with at least three anti-VEGF intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit
Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis
Availability of historical visual acuity data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
Availability of historical SD-OCT image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using ETDRS chart at a starting distance of 4 meters (see the BCVA manual for additional details) at screening and randomization visits
With any subtype of nAMD lesions (i.e., type I, type II, type III, or mixed forms per OCT classification, including polypoidal choroidal vasculopathy and retinal angiomatous proliferation)
Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical examination and analysis and grading by the central reading center of fundus photography (FP), FA, fundus autofluorescence (FAF) image, and SD-OCT images

Criterios de exclusión

Prior Ocular Treatment - Study Eye
History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
Prior pars plana vitrectomy surgery
Prior treatment with Visudyne® (verteporfin for injection), external-beam radiation therapy, or transpupillary thermotherapy
Previous treatment with corticosteroid intravitreal injection
Previous intraocular device implantation (not including intraocular lens implants)
Previous intraocular surgery (including cataract surgery) within 3 months of randomization
Previous laser (any type) used for AMD or diabetic retinopathy treatment
History of vitreous hemorrhage
History of rhegmatogenous retinal detachment
Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant
History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
History of corneal transplant
History of conjunctival surgery in the superotemporal quadrant (including pterygium surgery)
Prior Ocular Treatment Either Eye:
History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the ranibizumab or aflibercept injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anesthetic and antimicrobial preparations used by a subject during the study
Any contraindication to aflibercept as per local label
Prior participation in a clinical trial involving any anti-VEGF drugs within 6 months prior to the randomization visit
Prior treatment with brolucizumab (at any time prior to the screening visit)
Prior treatment with external-beam radiation therapy or brachytherapy
MNV (CNV) Lesion Characteristics Study Eye:
Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5-disc area (1.27 mm\^2) in size at screening
Subfoveal fibrosis or subfoveal atrophy
MNV (CNV) Lesion Characteristics Either Eye:
CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio retinopathy, or pathologic myopia
CNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)
Concurrent Ocular Conditions Study Eye :
Subfoveal and/or juxtafoveal retinal pigment epithelial tear
Scleral pathology in the superotemporal quadrant (e.g., scleral thinning or calcification)
Conjunctival pathologies (e.g., pterygium, scarring, thinning, fibrosis) in the superotemporal quadrant
Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, epiretinal membrane, amblyopia, or strabismus) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results
Active intraocular inflammation (grade trace or above)
Rhegmatogenous retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within 3 months prior to the randomization visit
Aphakia or absence of the posterior capsule Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of yttrium-aluminum garnet (YAG) laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia or evidence of pathologic myopia on depressed fundus exam
Preoperative refractive error that exceeds 8 diopters of myopia, for subjects who have undergone prior refractive or cataract surgery in the study eye
Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia
Preoperative refractive error that exceeds 5 diopters of hyperopia, for subjects who have undergone prior refractive or cataract surgery
Uncontrolled ocular hypertension or glaucoma (defined as intraocular pressure \[IOP\] \> 25 mmHg or a cup to disc ratio \> 0.8, despite treatment with anti-glaucoma medication) and any such condition the investigator determines may require a glaucoma-filtering surgery during a subject's participation in the study
History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis
Ectropion, entropion, ingrowing lashes, or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure
Trichiasis
Corneal neuropathy
Lagophthalmos or incomplete blink
Active or history of facial nerve palsy/paresis
Concurrent Ocular Conditions Non-Study (Fellow) Eye
Non-functioning non-study eye, defined as either:
BCVA of hand motion or worse
No physical presence of non-study eye (i.e., monocular)
Legally blind in the subject's relevant jurisdiction
Concurrent Ocular Conditions Either Eye
Any active or history of uveitis (e.g., idiopathic, drug-associated, or autoimmune-associated uveitis)
Active or history of keratitis, scleritis, endophthalmitis, or chronic blepharitis
Suspected or active ocular or periocular infectious conjunctivitis or endophthalmitis
Active or history of Sjogrens syndrome or keratoconjunctivitis sicca
Active or history of floppy eyelid syndrome
Active or history of chronic eye rubbing
Active thyroid eye disease
Concurrent Systemic Conditions:
Inability to comply with study schedule or procedures as described in the study protocol
Uncontrolled blood pressure (defined as systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 110 mmHg, while a subject is at rest) If a subject's initial measurement exceeds these values, a second reading should be taken ≥ 30 minutes after the first reading If the subject's blood pressure must be controlled by antihypertensive medication, the subject may become eligible if medication is taken continuously for at least 30 days prior to Day 1
Active or history of autoimmune diseases, for example, rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegner's)
History of stroke within the last 3 months prior to informed consent
Atrial fibrillation diagnosed or worsened within the last 3 months prior to informed consent
History of myocardial infarction within the last 3 months prior to informed consent
History of other disease, metabolic dysfunction (including uncontrolled diabetes), or clinical laboratory finding (after reviewing the results of the screening laboratory results) giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, aflibercept, or placement of the implant and that might affect interpretation of the results of the study or renders the subject at high risk of treatment complications in the opinion of the investigator
Confirmed active systemic infection
Use of any systemic anti-VEGF agents
Chronic use of oral corticosteroids (\> 10 mg/day of prednisone or equivalent)
Active cancer within 12 months of randomization except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤ 6 and a stable prostate-specific antigen for \> 12 months
Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the randomization visit
Requirement for continuous use of any medications or treatments prohibited in the study
Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 3 months after the final intravitreal injection of ranibizumab or aflibercept, or 1 year after the last implant refill-exchange procedure

Intervenciones

drug

Ranibizumab

Ranibizumab will be administered at a dose of 100 mg/mL delivered via the PDS.

drug

Aflibercept

Aflibercept will be administered at a dose of 2 mg in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment

device

Port Delivery System with ranibizumab (PDS)

PDS is an investigation intraocular drug delivery device designed to continuously deliver anti-VEGF therapy.

A Phase IIIb, Multicenter, Randomized, Visual Assessor-Masked Study Of The Effectiveness And Safety Of A 36-Week Refill Regimen For The Port Delivery System With Ranibizumab Vs Aflibercept Treat & Extend In Subjects With Neovascular Age-Related Macular Degeneration