Comparing Intravitreal Aflibercept Monotherapy vs Aflibercept Combined With Reduced Fluence PDT in PCV Treatment

A Multi-center Randomized Clinical Trial Comparing Intravitreal Aflibercept Monotherapy vs Aflibercept Combined With Reduced Fluence PDT for the Treatment of Polypoidal Choroidal Vasculopathy

In this study, we aim to evaluate the efficacy and safety of an individualized dosing schedule comprising Aflibercept and RF-PDT in patients with polypoidal choroidal vasculopathy (PCV). The primary objective is to compare the polyp closure rate at week 12 between the 2 treatment groups. The secondary aims include comparing visual, anatomical, treatment burden and clinical biomarkers between each treatment group.

Study Overview

• Status: Active, not recruiting
• Conditions: Polypoidal Choroidal Vasculopathy
• Intervention / Treatment: Drug: Aflibercept + reduced fluence photodynamic therapy (RF-PDT); Drug: Aflibercept + sham reduced fluence photodynamic therapy (RF-PDT)

Detailed Description

Age related macular degeneration (AMD) is one of the leading causes of blindness worldwide. In its exudative or wet form, choroidal neovascularization (CNV) causes an exudative maculopathy resulting in sudden loss of vision with severe effects on patients' quality of life. Intravitreal injections of anti-vascular endothelial growth factor agents (anti-VEGF) have become the mainstay of treatment for AMD CNV and has been shown to have favorable outcomes in most AMD CNV subtypes. In the Asian population, however, a particular subtype called polypoidal choroidal vasculopathy (PCV), which affects about 50% of exudative maculopathy, has been shown to have less favorable response to anti-VEGF therapy.

The best treatment option for PCV has remained unclear. Current best evidence is from 2 recent randomized controlled trials, the EVEREST II trial which compares the efficacy of ranibizumab with or without photodynamic therapy (PDT) for treatment of PCV and the PLANET trial which compares Aflibercept monotherapy against a rescue PDT when Aflibercept is deemed ineffective. Both trials have reported significant improvement in visual outcomes, however there remain significant unanswered questions and unmet needs regarding the use of Aflibercept and PDT as the best treatment for PCV.

In this study, we aim to compare the efficacy of combination Aflibercept with RF-PDT (at baseline) and Aflibercept monotherapy. This particular strategy has not been studies before and represents the amalgamation of unanswered questions from the best evidence to date for the treatment of PCV.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gemmy Cheung Chui Ming; Phone Number: 63227460; Email: gemmy.cheung.c.m@singhealth.com.sg
• Study Contact Backup: Name: Kelvin Teo Yi Chong

Study Locations

• Singapore
  • Singapore, Singapore
    • National University Hospital
  • Singapore, Singapore, 168751
    • Singapore National Eye Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged over 50 years old at the time of informed consent.
• Provide written informed consent.
• Willingness and ability to comply with all scheduled visits and study procedures.
• Confirmed diagnosis of symptomatic macular PCV based ICGA.

• Activity of PCV confirmed by exudative activity involving the macula on OCT or Fluorescein Angiography (FA) or both.

  • Presence of intra retinal or subretinal fluid/blood as seen on OCT

  • Treatment naïve

    • NO previous treatment with intravitreal anti-VEGF agents, regardless of the indication
    • NO previous thermal laser in the macular region, or verteporfin photodynamic therapy (vPDT), regardless of indication
    • NO other previous treatment for neovascular AMD (nAMD), except oral supplements and traditional Chinese medicine
• An ETDRS BCVA of at least 4 letters (Snellen equivalent approximately 20/800 or better) in the study eye.
• Greatest Linear Dimension (GLD) of the total lesion area (BVN + polyps) <5400µm (~9 mucopolysaccharidoses (MPS) Disc Areas) as delineated by ICGA.

Exclusion Criteria: - Participant

• 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).
• Participation in an investigational trial within 30 days of enrollment which involves treatment with unapproved investigational drug.
• Known allergy to any component of the study drug.
• 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.
• 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.
• Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.
• Amblyopia or blind in one eye Study Eye
• Eye with intra retinal or sub-retinal fluid due to other causes than PCV
• 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 Macular Edema (DME), vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)
• 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).
• Any intraocular surgery within 1 month of enrollment
• Treatment with intra vitreal corticosteroids
• History of retinal detachment or surgery for retinal detachment
• History of vitrectomy
• History of macular hole
• Evidence of vitreomacular traction that may preclude resolution of macular edema > 4 disc areas of intra/sub retinal hemorrhage
• Aphakia
• Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis

Other Eye

• Active intraocular inflammation
• History of uveitis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aflibercept + RF-PDT; Patients with symptomatic macular PCV (n=80) as confirmed by Indocyanine green Angiography(ICGA) will be treated with Aflibercept (dosage=2mg/0.05ml) through an intravitreal injection + RF-PDT ( 6mg/m2 intravenous infusion of Verteporfin followed by laser light at a dose rate of 25 Joules/cm2) at baseline. Aflibercept- 1st treatment (baseline) followed by minimum retreatment interval of 4 weeks (from Baseline to week 8) and then retreatment at intervals of 4 weeks pro re nata (PRN) retreatment( week 12-48). Primary endpoint at week 52. RF-PDT treatment at baseline followed by pro re nata (PRN) at 12 week intervals. At each visit, subjects will be assessed based on BCVA, ophthalmic examination and Optical Coherence Tomography (OCT)	Drug: Aflibercept + reduced fluence photodynamic therapy (RF-PDT); Aflibercept dosage of 2mg in 0.05ml along with intravenous infusion of Verteporfin (6mg/m2)followed by laser light at a dosage of 25Joule/cm2; Other Names: Eylea; Visudyne
Active Comparator: Aflibercept + sham RF-PDT; Patients with symptomatic macular PCV (n=80) as confirmed by Indocyanine green Angiography(ICGA) will be treated with Aflibercept (dosage=2mg/0.05ml) through an intravitreal injection, at baseline. A minimum of 1 injection(baseline) followed by minimum pro re nata (PRN) retreatment interval of 4 weeks ( from baseline to week 8) and then a minimum of 4 weeks retreatment thereafter (week 12-48). Primary endpoint at week 52. Sham RF-PDT treatment at baseline followed by pro re nata (PRN) at 12 week intervals. At each visit, subjects will be assessed based on Best Corrected Visual Acuity (BCVA), ophthalmic examination and Optical Coherence Tomography (OCT)	Drug: Aflibercept + sham reduced fluence photodynamic therapy (RF-PDT); Aflibercept dosage of 2mg in 0.05ml along with sham photodynamic therapy; Other Names: Eylea

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Polyp Closure rate	polyp closure rate at week 12 between the 2 treatment groups.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optical Coherence Tomography	For evidence of intraretinal or subretinal fluid, ill-defined hyper-reflective material and/or new hemorrhage	12 months
Optical Coherence Tomography-Angiograph	For evidence of intraretinal or subretinal fluid, ill-defined hyper-reflective material and/or new hemorrhage	12 months
Color Fundus photography	inspect anomalies associated to diseases that affect the eye, and to monitor their progression	baseline, month 3, month12
Autofluorescence Photography	Retinal imaging	baseline, month 3, month12
Fundus Fluorescein Angiography	Retinal circulation	Baseline, month 3, month 12
Intra Ocular Pressure (IOP)	Fluid Pressure in eye	Baseline, 12 months

Collaborators and Investigators

• Sponsor: Singapore National Eye Centre
• Collaborators: National University Hospital, Singapore; Tan Tock Seng Hospital
• Investigators: Principal Investigator: Gemmy Cheung Chui Ming, Singapore National Eye Centre

Publications and helpful links

General Publications

• Vyas CH, Cheung CMG, Tan C, Chee C, Wong K, Jordan-Yu JMN, Wong TY, Tan A, Fenner B, Sim S, Teo KYC. Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy. BMJ Open. 2021 Jul 15;11(7):e050252. doi: 10.1136/bmjopen-2021-050252.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: April 24, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Eye Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Neovascularization, Pathologic; Choroidal Neovascularization; Vascular Diseases; Polypoidal Choroidal Vasculopathy; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: R1735/58/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No