Efficacy and Safety of Verteporfin Added to Ranibizumab in the Treatment of Symptomatic Macular Polypoidal Choroidal Vasculopathy

Study Overview
=================
Brief Summary
-----------------
This study aims to compare the efficacy of ranibizumab and verteporfin PDT combination treatment and verteporfin PDT monotherapy vs.ranibizumab monotherapy alone in achieving complete regression of polyps in patients with symptomatic macular polypoidal choroidal vasculopathy.

Official Title
-----------------
A Multicentre, Randomized, Double Masked, Exploratory, Indocyanine Green Angiography (ICGA) Guided Study of 6 Months Duration to Compare the Safety and Effect on Polyp Regression of Verteporfin Photodynamic Therapy (PDT) Alone or Added to Ranibizumab in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy

Conditions
-----------------
Polypoidal Choroidal Vasculopathy

Intervention / Treatment
-----------------
* Drug: Verteporfin Photodynamic Therapy
* Drug: Ranibizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must give written informed consent before any assessment is performed. Male or Female patients ≥18 yrs of age Patients willing and able to comply with all study procedures Inclusion criteria for study eye: BCVA letter score between 73-24 (approximately 20/40 to 20/320 Snellen equivalent) using ETDRS visual acuity chart measured at 4 meters PCV diagnosis confirmed by Central Reading Center Greatest Linear Dimension (GLD) of the total lesion area < 5400 µm ( 9 Macular Photocoagulation Study Disc Areas) Exclusion Criteria: Women of child-bearing potential who are not using one or more reliable contraception methods Pregnant or nursing (lactating) women History of hypersensitivity or allergy to fluorescein or indocyanine green (ICG), clinically significant drug allergy or known hypersensitivity to therapeutic or diagnostic protein products, or to any of the study drugs or their components Patient with history of porphyria Systemic medications known to be toxic to the lens, retina, or optic nerve History of which might affect the interpretation of the results of the study, or renders the patient at high risk from treatment complications Use of other investigational drugs within 30 days of randomization Exclusion criteria for study eye: Concomitant conditions/diseases: Presence of angioid streaks, macular fibrosis, presumed ocular histoplasmosis syndrome, pathologic myopia (-8 Diopters or more) Active ocular inflammation or infection Uncontrolled glaucoma Ocular disorders that may confound interpretation of study results Prior Ocular treatment: Prior Verteporfin PDT, external-beam radiation, laser photocoagulation, macular surgery, or transpupillary thermotherapy Prior local treatment with Pegaptanib, Ranibizumab, Bevacizumab or other anti-angiogenic compound or any investigational treatment in both eyes or systemic use of bevacizumab within 90 days prior to randomization History of intraocular surgery including pars plana vitrectomy and intraocular hemorrhage displacement is not allowed with the exception of uncomplicated cataract surgery that is allowed within 60 days prior to screening Ocular conditions that required chronic concomitant therapy within 90 days prior to randomization with topical, ocular, or systemically administered corticosteroids or any herbal medication known to contain steroid-like components Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verteporfin and Ranibizumab<br>Photodynamic therapy with verteporfin in combination with ranibizumab injection. Patients received one treatment at baseline with verteporfin photodynamic therapy (PDT) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, light application of 50 J/cm^2 to the study eye was begun 15 minutes after the start of infusion.<br>* Other names: Visudyne;Drug: Ranibizumab<br>* Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;|
| Active Comparator: Verteporfin monotherapy<br>Patients received one treatment at baseline with verteporfin photodynamic therapy in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab placebo (sham intravitreal injection) on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, light application of 50 J/cm^2 to the study eye was begun 15 minutes after the start of infusion.<br>* Other names: Visudyne;|
| Active Comparator: Ranibizumab monotherapy<br>Patients received one treatment at baseline with verteporfin placebo (with sham photodynamic therapy) in the study eye and thereafter based on re-treatment criteria at intervals of at least 90 days. Within 1-24 hours, patients also received Ranibizumab intravitreal injection on Day 1 and at Month 1 and 2 and thereafter according to the re-treatment criteria at intervals of at least 30 days through Day 150. From month 3 onward, re-treatments were determined based on study-specific re-treatment criteria that included evaluation of polyp progression on indocyanine green angiography (ICGA), and assessment of fluorescein angiograms and visual acuity. | Drug: Ranibizumab<br>* Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA) | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA | Indocyanine green angiography (ICGA) assessments were performed using the Heidelberg Retinal Angiography 2 (HRA2) machine to measure the Total Lesion Area and the degree of polyp regression. Complete regression was defined as no polyps seen on the imaging. | Baseline through end of study (6 months) | 
| Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT) | High resolution 6 meridian scans were performed to measure central retinal thickness. | Baseline and Month 6 | 
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6 | BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity. | Baseline and Month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polypoidal choroidal vasculopathy, PCV, Age-related macular degeneration (AMD) variant, vision, polyps, indocyanine green angiography, verteporfin, ranibizumab, photodynamic therapy