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

NCT00674323 | Completed Phase 4 Results

• 1 other identifier: CBPD952A2209
• Study Type: interventional
• Target: 61
• Locations: 5 countries
• Sites: 5

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.

Conditions

Polypoidal Choroidal Vasculopathy

Keywords

Polypoidal choroidal vasculopathy; PCV; Age-related macular degeneration (AMD) variant; vision; polyps; indocyanine green angiography; verteporfin; ranibizumab; photodynamic therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of Participants With at Least One Complete Polyp Regression During 6 Months Assessed by ICGA

  Baseline through end of study (6 months)

• Mean Change From Baseline in Central Retinal Thickness Measured by Optic Coherence Tomography (OCT)

  Baseline and Month 6

• Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye at Month 6

  Baseline and Month 6

Study Arms (3)

Verteporfin and Ranibizumab

EXPERIMENTAL

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; Drug: Ranibizumab

Verteporfin monotherapy

ACTIVE COMPARATOR

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

Ranibizumab monotherapy

ACTIVE COMPARATOR

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

Interventions

Verteporfin Photodynamic Therapy DRUG

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.

Also known as: Visudyne

Verteporfin and Ranibizumab; Verteporfin monotherapy

Ranibizumab DRUG

Ranibizumab at dose of 0.5 mg administered as an intravitreal injection.

Also known as: Lucentis

Ranibizumab monotherapy; Verteporfin and Ranibizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis: lead

Study Sites (5)

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Singapore, Singapore

Location

Novartis Investigative Site

Seoul, South Korea

Location

Novartis Investigative Site

Taipei, Taiwan

Location

Novartis Investigative Site

Bangkok, Thailand

Location

Related Publications (2)

• 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.

  PMID: 25758601 DERIVED

• 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.

  PMID: 22426346 DERIVED

MeSH Terms

Conditions

Polypoidal Choroidal Vasculopathy; Macular Degeneration; Polyps

Interventions

Verteporfin; Ranibizumab

Condition Hierarchy (Ancestors)

Choroidal Neovascularization; Choroid Diseases; Uveal Diseases; Eye Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Retinal Degeneration; Retinal Diseases; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: May 7, 2008
• Study Start: April 1, 2008
• Primary Completion: May 1, 2009
• Last Updated: April 19, 2011
• Results First Posted: January 25, 2011

Record last verified: 2011-04

Locations

KR (1); HK (1); SG (1); TH (1); TW (1)