Randomized, Double-masked, Sham-controlled Phase 4 Study, Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Monotherapy Compared to Aflibercept With Adjunctive Photodynamic Therapy in Patients With Polypoidal Choroidal Vasculopathy

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy and safety of intravitreal Aflibercept monotherapy with the efficacy and safety of combined treatment with Aflibercept plus standard photodynamic therapy (PDT) with Verteporfin in age-related macular degeneration (AMD) patients with polypoidal choroidal vasculopathy (PCV).

Detailed Description
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To compare the efficacy and safety of intravitreal Aflibercept monotherapy with the efficacy and safety of combined treatment with Aflibercept associated with standard photodynamic therapy (PDT) with Verteporfin in age-related macular degeneration (AMD) patients with polypoidal choroidal vasculopathy (PCV) in a proof concept study and to identify genetic biomarkers for the diagnosis and treatment response of PCV in Caucasians.

Official Title
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A Randomized, Double-masked, Sham-controlled Phase 4 Study of the Efficacy, Safety, and Tolerability of IV Aflibercept Monotherapy Compared to Aflibercept With Adjunctive Photodynamic Therapy in Patients With PCV.

Conditions
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Polypoidal Choroidal Vasculopathy

Intervention / Treatment
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* Drug: Intravitreal Aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either gender and Age ≥ 50. Naïve PCV patients. Confirmed diagnosis of symptomatic macular PCV in the study eye. Greatest linear dimension of the lesion of < 5400 mm, assessed by ICG angiography. BCVA at study entry of 25 to 80 letters (Snellen Equivalent 20/320 to 20/25). Lesion size in the study eye at study entry: Presence of PCV assessed by the Central Reading Centre based on ICG with active polyps with or without abnormal vascular network. Women must be using effective contraception, be post-menopausal for at least months prior to trial entry, or surgically sterile. Ability to provide written informed consent. Ability to return for all study visits. Exclusion Criteria: Active inflammation or infection in the study eye. Uncontrolled intraocular pressure in the study eye. Ocular condition in the study eye which may impact vision and confound study outcomes (e.g. vitreomacular traction, epirretinal membrane with BCVA impact, ocular inflammation, retinal vascular diseases like diabetic retinopathy or diabetic macular edema). Presence of centromacular scarring or atrophy indicating irreversible BCVA loss. Prior treatment of the study eye with anti-VEGF therapy or systemic use of anti-VEGF products within 3 months prior to the study entry. Previous vitrectomy, macular laser treatment, PDT, or intraocular steroids in the study eye.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Aflibercept Monotherapy<br>IVT Aflibercept 2 mg + Sham PDT | Drug: Intravitreal Aflibercept<br> <br> * Other names: standard photodynamic therapy (PDT);|
| Active Comparator: Aflibercept + verteporfin PDT<br>IVT Aflibercept 2 mg + Verteporfin PDT | Drug: Intravitreal Aflibercept<br> <br> * Other names: standard photodynamic therapy (PDT);|

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) | Unit of Measure: [Letters] | from Baseline (Week 0) to Week 52. | 
| Polyps regression | Unit of Measure: [Yes, No] | from Baseline (W0) to Week 52. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polyps regression, assessed by Indocyanine Green Angiography (ICGA); | Unit of Measure: [Yes, No] | from Baseline (W0) to Week 16 | 
| Presence of active polyps, assessed by Indocyanine Green Angiography (ICGA); | Unit of Measure: [Yes, No] | from Baseline (W0) to Week 52 | 
| Presence of leakage based on fluorescein angiography (FA) | Unit of Measure: [Yes, No] | from Baseline (W0) to Week 52 | 
| Change in the Subfield Central Retinal Thickness (CRT), assessed by Spectral Domain-Optical Coherence Tomography (SD-OCT); | Unit of Measure: [µm] | from Baseline (W0) to Week 52 | 
| Presence of fluid assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT) at Week 52; | Unit of Measure: [Yes, No] | from Baseline (W0) to Week 52 | 
| Total number of treatments with Aflibercept; | Unit of Measure: [#] | from Baseline (W0) to Week 52 | 
| Frequency and severity of ocular and non-ocular adverse events over time. | Unit of Measure: [Mild, Moderate, Severe] | from Baseline (W0) to Week 52 |