A Study to Learn How Well Aflibercept Injected Into the Eye Works and How Safe it is When Given in Customized Treatment Intervals in Patients With an Eye Disease Called Neovascular Age-related Macular Degeneration After Start of Treatment

Study Overview
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Brief Summary
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Researchers are looking for a better way to treat people who have neovascular (wet) age-related macular degeneration (nAMD or wet AMD). In people with wet AMD, the body makes too much of a protein called vascular endothelial growth factor (VEGF). This causes too many blood vessels to grow in the area of sharpest vision in the eye, called macula. Fluid buildup due to leakage from these vessels can damage the macula, leading to vision problems such as blurring or a blind spot in the central (straight ahead) vision needed for reading or face recognition or car driving. Wet AMD is common in people aged 50 and older. The study treatment intravitreal aflibercept (also called BAY865321) is injected into the eye. It works by blocking the VEGF protein and thus reduces blood vessel growth. It has already been approved for patients with wet AMD to be given as intravitreal injection monthly at start and then every 8 weeks or longer. Repeated injections of aflibercept prevent worsening of vision but place a burden on the patient. Doctors try to increase the time between injections (treatment interval) in routine clinical practice based on individual patient needs. This is called treat and extend (T&E). Treatment intervals are stepwise extended or shortened depending on how the treatment works. This is checked with optical coherence tomography (OCT), an imaging technique used to observe relevant changes in the eye. The main purpose of this study is to learn how well aflibercept works if treatment intervals are extended faster (timepoint of extension is the same for both treatments arms), compared to standard T&E regimen in people with wet AMD in a preselected patient population with no fluid after treatment initiation. To answer this, researchers will assess changes in vision called best corrected visual acuity (BCVA) between study start and after 36 weeks. Changes will then be compared between participants whose treatment intervals were extended early and those on standard T&E regimen. All participants will receive 2 mg aflibercept as intravitreal injection for up to 52 weeks in intervals of every 4 to 16 weeks. Each participant will be in the study for up to 56 weeks. During this time 4 visits to the study site are set for all participants. The other visits are set individually. A final phone call is planned 3 days after treatment at the end of study. During the study, the doctors and their study team will: check patients' eye health using various eye examination techniques (slit lamp microscopy, OCT, and ophthalmoscopy) that may necessitate eye drops to widen the pupil) measure patients' eye vision (BCVA) do physical examinations check vital signs ask the participants questions about how they are feeling and what adverse events they are having. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments. In addition, participants in the fast extension arm will be provided with a home monitoring OCT device.

Official Title
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A Parallel-group Phase 4, Open-label, Two-arm Study to Assess the Safety and Efficacy of Intravitreal (IVT) Aflibercept With Proactive Customized Treatment Intervals in Patients ≥50 Years of Age With No Fluid Due to Choroidal Neovascularization (CNV) Lesions Secondary to Neovascular (Wet) Age-related Macular Degeneration (nAMD) Following Treatment Initiation With Aflibercept

Conditions
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Neovascular (Wet) Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Aflibercept(BAY86-5321, Eylea)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent and able to read (or if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member), understand, and willing to sign the informed consent form (ICF). Men and women ≥50 years of age. At treatment initiation, active macular neovascular lesions secondary to nAMD (Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the electronic case report form [eCRF]). Treatment initiation with 3 × monthly IVT aflibercept injections (Weeks -16, -12, and -8 to planned study baseline visit) resulting in absence of any fluid at week -8. ETDRS BCVA of at least 25 letters (20/320 Snellen equivalent) in the study eye at screening visit. Willing, committed, and able to return for all clinic visits and complete all study-related procedures. Able to use the provided monitoring device and willing to perform 5 × weekly self-assessments in the Investigator's opinion. Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period between signing of the ICF and 3 months after the last administration of study drug. Exclusion Criteria: Any contraindication to IVT anti-vascular endothelial growth factor (VEGF) treatment or treatment with Eylea® as detailed in the Summary of Product Characteristics (SmPC). Any prior ocular (in the study eye) or systemic treatment (including investigational agents) or surgery for nAMD, except the 3 × monthly IVT aflibercept injections required for treatment initiation and dietary supplements or vitamins. Any presence of intraretinal and subretinal fluid. Any ocular or systemic condition expected to interfere with study outcomes and procedures, including but not limited to: Scar, fibrosis or other lesions (e.g., retinal pigment epithelium [RPE] tears, macular hole stage 2 or above and others) involving the center of the macula in the study eye. Clinically relevant opacities or conditions involving the optic media including cataract, corneal dystrophies or s.p. corneal transplant in the study eye. Uncontrolled glaucoma (defined as IOP ≥25 mm Hg despite treatment with antiglaucoma medication) in the study eye or prior trabeculectomy or other filtration surgery in the study eye. Intraocular surgery, periocular surgery, or cataract surgery within 90 days before Day 1 in the study eye, except the IVT aflibercept injections required for treatment initiation and any history of vitrectomy, retinal radiation therapy, retinal detachment or treatment or surgery for retinal detachment in the study eye. Aphakia or pseudophakia with absence of posterior capsule (unless as a result of an yttrium aluminum garnet posterior capsulotomy) in the study eye. Participation as a patient in any clinical study within 12 weeks before screening. Close affiliation with the investigational site; e.g., a close relative of the Investigator, dependent person (e.g., employee or student of the investigational site). Previously screen failed patients for this study.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Customized treatment interval<br>After the initial study injection at baseline, participants will receive their next study injection at Week 16. Participants in this study arm will also be issued a home monitoring device, which will allow for regular OCT monitoring (at least 5 times a week) at home. | Drug: Aflibercept(BAY86-5321, Eylea)<br>* 2mg, intravitreal (IVT) injection<br>|
| Active Comparator: Treat and extend (T&E) 2 week adjustment<br>Participants will receive treatment in intervals maintained (8 weeks) or adjusted in 2 weeks increments each time (up to a maximum of 16 weeks and minimum of 4 weeks), as long as all extension/shortening criteria are met. | Drug: Aflibercept(BAY86-5321, Eylea)<br>* 2mg, intravitreal (IVT) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in best-corrected visual acuity (BCVA) | BCVA is measured by the early treatment diabetic retinopathy study (ETDRS) letter score for the study eye | From baseline to Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of IVT aflibercept injections per patient |  | From baseline up to Week 52 | 
| Number of IVT aflibercept injections per patient |  | From baseline up to Week 36 | 
| Number of patients achieving pre-defined treatment intervals (≥4, ≥8, ≥10, ≥12¸ ≥14, and 16 weeks) |  | At Week 36 and Week 52 | 
| Change in best-corrected visual acuity (BCVA) | BCVA is measured by the early treatment diabetic retinopathy study (ETDRS) letter score for the study eye | From baseline up to Week 52 | 
| Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) |  | From baseline up to Week 36 and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aflibercept, Anti-vascular endothelial growth factor, Treatment interval extension