An Open Label-study to Compare the Efficacy of Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy
Condition: Age Related Macular Degeneration; Polypoidal Choroidal Vasculopathy
MeSH terms: Macular Degeneration; Polypoidal Choroidal Vasculopathy; Vascular Diseases
Intervention: Treat and Extend with Aflibercept 2mg; Fixed Dosing with Aflibercept 2mg
Intervention description: Drug treatment regime which allows extension of treatment interval based on disease activity; Fixed 8 weekly dosing regime throughout the study duration
Intervention MeSH terms: Aflibercept
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective, 2-arm, Non-inferiority, interventional study
Masking: None (Open Label)
Enrollment: 54.0
Sex: All
Minimum age: 45 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: anti vegf; aflibercept; treat and extend

Summary:

      Polypoidal choroidal neovasculopathy (PCV) is a subtype of wet age related macula
      degeneration (AMD) occuring more commonly in the Asian population. Besides the phenotypic
      differences, PCV is thought to have a lesser response to anti VEGF therapy which is the
      mainstay of treatment for other typical wet AMD. Recent trial data suggest that a combination
      with photodynamic therapy may help in the visual and anatomical outcome of PCV, and emerging
      evidence shows favourable outcomes the newer anti VEGF agent, aflibercept 2mg monotherapy.
      These trials however, have assessed aflibercept in a strict 2mg every 8 weekly regime.

      In the clinical setting, a significant an unmet need in the management of PCV is a tailored
      treatment regime. Here we propose a treatment regimen based on disease activity for PCV with
      aflibercept mono therapy. A limitation of the 2q8 regime is that it is fixed and does not
      vary regardless of polyp closure or anatomical outcome at the first time point of assessment
      (month 3). We hypothesize that after the initial 3 monthly injections of aflibercept, about
      50% of PCV will close and become quiescent, and in the remaining 50%, a further 3 monthly
      injections will increase overall polyp closure rate. After a loadings phase of either 3 or 6
      months, all eyes will start on a treat and extend regime (T&E), with a minimum period of 8
      weeks and a maximum of 12 weeks between treatments with 2 week increments if PCV remains
      quiescent. The proposed study aims to evaluate the efficacy of a modified treat and extend
      regime based on disease activity with aflibercept monotherapy for PCV.
    

Eligibility criteria:

        Inclusion Criteria Participant

          1. Male or female study participants, age >=45 years of age at the time of informed
             consent.

          2. Best corrected ETDRS visual acuity score <= 78 (ie 20/32 or worse)

          3. Diagnosis of PCV based on ICGA

               1. Presence of intra retinal or subretinal fluid/blood at the fovea as seen on OCT

               2. Treatment naïve

          4. Media clarity, pupillary dilation and individual cooperation sufficient for study
             procedure including fundus photography.

          5. Able and willing to provide informed consent.

        1.2. Exclusion Criteria Participant

          1. Medical condition that, in the opinion of the investigator, would preclude
             participation in the study (e.g.unstable medical status including blood pressure,
             cardiovascular disease, and glycemic control).

          2. Participation in an investigational trial within 30 days of enrolment which involves
             treatment with unapproved investigational drug

          3. Known allergy to any component of the study drug.

          4. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110 on repeated
             measurements). If blood pressure is brought below 180/110 by anti-hypertensive
             treatment, individual can become eligible.

          5. Myocardial infarction, other acute cardiac event requiring hospitalization, stroke,
             transient ischemic attack, or treatment for acute congestive heart failure within 4
             months prior to randomization.

          6. Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or
             anticipated use during the study.

        Study Eye

          1. Eye with intra retinal or subretinal fluid due to other causes than PCV

          2. An ocular condition is present (other than PCV) that, in the opinion of the
             investigator, might affect intra or sub retinal fluid or alter visual acuity during
             the course of the study (e.g., diabetic macula edema (DME), vein occlusion, uveitis or
             other ocular inflammatory disease, neovascular glaucoma, etc.)

          3. Substantial cataract that, in the opinion of the investigator, is likely to be
             decreasing visual acuity by more than three lines (i.e., cataract would be reducing
             acuity to worse than 20/40 if eye was otherwise normal).

          4. Any intraocular surgery within 3 months of enrollment

          5. Treatment with intra vitreal corticosteroids

          6. History of retinal detachment or surgery for retinal detachment

          7. History of vitrectomy

          8. History of macular hole

          9. Evidence of vitreomacular traction that may preclude resolution of macular edema > 4
             disc areas of intra/sub retinal hemorrhage

         10. Aphakia

         11. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or
             significant blepharitis

        Other Eye

          1. Active intraocular inflammation

          2. History of uveitis