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

Primary Purpose

Polypoidal Choroidal Vasculopathy

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Verteporfin Photodynamic Therapy
Ranibizumab
Sponsored by
Novartis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polypoidal Choroidal Vasculopathy focused on measuring Polypoidal choroidal vasculopathy, PCV, Age-related macular degeneration (AMD) variant, vision, polyps, indocyanine green angiography, verteporfin, ranibizumab, photodynamic therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Verteporfin and Ranibizumab

Verteporfin monotherapy

Ranibizumab monotherapy

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
May 5, 2008
Last Updated
April 15, 2011
Sponsor
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00674323
Brief Title
Efficacy and Safety of Verteporfin Added to Ranibizumab in the Treatment of Symptomatic Macular Polypoidal Choroidal Vasculopathy
Acronym
PCV
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2011
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polypoidal Choroidal Vasculopathy
Keywords
Polypoidal choroidal vasculopathy, PCV, Age-related macular degeneration (AMD) variant, vision, polyps, indocyanine green angiography, verteporfin, ranibizumab, photodynamic therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Verteporfin and Ranibizumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Verteporfin monotherapy
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Ranibizumab monotherapy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Verteporfin Photodynamic Therapy
Other Intervention Name(s)
Visudyne
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.
Primary Outcome Measure Information:
Title
Number of Participants With Complete Regression (CR) of Polyps Measured by Indocyanine Green Angiography (ICGA)
Description
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.
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA
Description
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.
Time Frame
Baseline through end of study (6 months)
Title
Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT)
Description
High resolution 6 meridian scans were performed to measure central retinal thickness.
Time Frame
Baseline and Month 6
Title
Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6
Description
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.
Time Frame
Baseline and Month 6

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis
Official's Role
Study Chair
Facility Information:
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Seoul
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
Country
Singapore
Facility Name
Novartis Investigative Site
City
Taipei
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
25758601
Citation
Tan CS, Ngo WK, Chen JP, Tan NW, Lim TH; EVEREST Study Group. EVEREST study report 2: imaging and grading protocol, and baseline characteristics of a randomised controlled trial of polypoidal choroidal vasculopathy. Br J Ophthalmol. 2015 May;99(5):624-8. doi: 10.1136/bjophthalmol-2014-305674. Epub 2015 Mar 10.
Results Reference
derived
PubMed Identifier
22426346
Citation
Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, Lai TY, Pilz S, Ruamviboonsuk P, Tokaji E, Weisberger A, Lim TH. EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina. 2012 Sep;32(8):1453-64. doi: 10.1097/IAE.0b013e31824f91e8.
Results Reference
derived

Learn more about this trial

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

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