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

NCT ID: NCT00674323

Last Updated: 2011-04-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Verteporfin and Ranibizumab

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.

Group Type: EXPERIMENTAL

Verteporfin Photodynamic Therapy

Intervention Type: 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.

Ranibizumab

Intervention Type: DRUG

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

Verteporfin monotherapy

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.

Group Type: ACTIVE_COMPARATOR

Verteporfin Photodynamic Therapy

Intervention Type: 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.

Ranibizumab monotherapy

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.

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

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

Interventions

Verteporfin Photodynamic Therapy

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

Ranibizumab

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

Intervention Type: DRUG

Other Intervention Names

Visudyne; Lucentis

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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: lead

Responsible Party

Novartis

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_CHAIR

Novartis

Locations

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Bangkok, , Thailand

Countries

Hong Kong; Singapore; South Korea; Taiwan; Thailand

References

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.

Reference Type: DERIVED

PMID: 25758601 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22426346 (View on PubMed)

Other Identifiers

CBPD952A2209

Identifier Type: -

Identifier Source: org_study_id