Study to Gather Information on Safety and Use of High Dose Aflibercept Injection Into the Eye in Patients With an Age Related Eye Disorder That Causes Blurred Vision or a Blind Spot Due to Abnormal Blood Vessels That Leak Fluid Into the Light Sensitive Lining Inside the Eye

Study Overview
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Brief Summary
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In this study researchers want to learn more about changes in visual acuity (clarity of vision) with a high dose treatment with Aflibercept (Eylea) in patients suffering from neovascular age-related macular degeneration (nAMD). Neovascular AMD is an eye disease that causes blurred vision or a blind spot due to abnormal blood vessels that leak fluid or blood into the light sensitive lining inside the eye (retina). The fluid buildup causes the central part of the retina (macula) responsible for sharp, straight-ahead vision to swell and thicken (edema), which distorts vision.

Official Title
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Randomized, Double-Masked, Active-Controlled, Phase 3 Study of the Efficacy and Safety of High Dose Aflibercept in Patients With Neovascular Age-Related Macular Degeneration

Conditions
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Neovascular Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)
* Drug: Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active subfoveal CNV secondary to nAMD, including juxtafoveal lesions that affect the fovea as assessed in the study eye. Total area of CNV (including both classic and occult components) must comprise greater than 50% of the total lesion area in the study eye. BCVA ETDRS letter score of 78 to 24 (corresponding to a Snellen equivalent of approximately 20/32 to 20/320) in the study eye. Decrease in BCVA determined to be primarily the result of nAMD in the study eye. Presence of IRF and/or SRF affecting the central subfield of the study eye on OCT. Contraceptive use by men or women should be consistent with local regulations regarding the methods of highly effective contraception for those participating in clinical studies. Other protocol-specified inclusion criteria. Additional inclusion criteria for Year 3: At least one BCVA value and one central subfield retinal thickness (CST) value from measurements at one of the following visits: Visit 24 (Week 84), Visit 25 (Week 88) or Visit 26 (Week 92). Participant is enrolled at a site that participates in the extension period. Exclusion Criteria: Causes of CNV other than nAMD in the study eye. Scar, fibrosis, or atrophy involving the central subfield in the study eye. Presence of retinal pigment epithelial tears or rips involving the central subfield in the study eye. Uncontrolled glaucoma (defined as IOP >25 mmHg despite treatment with anti-glaucoma medication) in the study eye. History of idiopathic or autoimmune uveitis in the study eye. Myopia of a spherical equivalent of at least 8 diopters in the study eye prior to any refractive or cataract surgery. History or clinical evidence of diabetic retinopathy, diabetic macular edema, or any retinal vascular disease other than nAMD in either eye. Evidence of extraocular or periocular infection or inflammation (including infectious blepharitis, keratitis, scleritis, or conjunctivitis) in either eye at the time of screening/randomization. Uncontrolled blood pressure (defined as systolic >160 mmHg or diastolic >95 mmHg). Any prior or concomitant ocular (in the study eye) or systemic treatment (with an investigational or approved, anti-VEGF or other agent) or surgery for nAMD, except dietary supplements or vitamins. Other protocol-specified exclusion criteria

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aflibercept 2q8<br>In the double-masked study part (Years 1 and 2), Aflibercept 2 mg administered every 8 weeks after a loading phase. (Active Comparator) In Year 3, high dose aflibercept administered according to individual patient response. (Experimental) | Drug: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)<br>* Solution in Vial, intravitreal (IVT) injection<br>Drug: Aflibercept VEGF Trap-Eye (Eylea, BAY86-5321)<br>* Solution in Vial, 2 mg, intravitreal (IVT) injection<br>|
| Experimental: Aflibercept HDq12<br>Aflibercept high dose (HD) administered every 12 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response. | Drug: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)<br>* Solution in Vial, intravitreal (IVT) injection<br>|
| Experimental: Aflibercept HDq16<br>Aflibercept high dose administered every 16 weeks after an initiation phase. Treatment intervals adjusted according to individual patient response. | Drug: Aflibercept High Dose VEGF Trap-Eye (BAY86-5321)<br>* Solution in Vial, intravitreal (IVT) injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 48 | Visual function of the study eye was assessed at a distance of 4 meters using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. BCVA scale range is 0 (worst) to 100 (best). | At baseline and Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in BCVA Measured by the ETDRS Letter Score at Week 60 |  | At baseline and Week 60 | 
| Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in Central Subfield at Week 16 |  | At Week 16 | 
| Percentage of Participants Gaining at Least 15 Letters in BCVA From Baseline at Week 48 |  | At baseline and Week 48 | 
| Percentage of Participants Achieving an ETDRS Letter Score of at Least 69 (Approximate 20/40 Snellen Equivalent) at Week 48 |  | At Week 48 | 
| Change in Choroidal Neovascularization (CNV) Size From Baseline to Week 48 |  | At baseline and Week 48 | 
| Change in Total Lesion Area From Baseline to Week 48 |  | At baseline and Week 48 | 
| Percentage of Participants With no Intraretinal Fluid (IRF) and no Subretinal Fluid (SRF) in the Center Subfield at Week 48 |  | At Week 48 | 
| Change From Baseline in Central Subfield Retinal Thickness (CST) at Week 48 |  | At baseline and Week 48 | 
| Change From Baseline in National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Total Score at Week 48 | NEI VFQ-25 was a 25-item questionnaire that gave a score on a scale from 0 (worst) to 100 (best = no vision problems) | At baseline and Week 48 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) |  | Up to 156 weeks | 
| Systemic Exposure to Aflibercept as Assessed by Plasma Concentrations of Free, Adjusted Bound and Total Aflibercept From Baseline Through Week 48 |  | Up to Week 48 | 
| Assessment of Immunogenicity to Aflibercept by Measuring the Incidence of Treatment-emergent Anti-drug Antibodies (ADA) Response Through End of Masked Study |  | Up to week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nAMD