Reduced Fluence Visudyne-Anti-VEGF-Dexamethasone In Combination for AMD Lesions (RADICAL) (RADICAL)

A Multicenter, Randomized, Single-masked Study Comparing Reduced-fluence Visudyne®-Lucentis® Combination Therapies and Lucentis® Monotherapy in Subjects With Choroidal Neovascularization (CNV) Secondary to AMD.

The objective of this study is to determine if combination therapy (reduced-fluence Visudyne followed by Lucentis [within 2 hours] or either of two regimens of reduced-fluence Visudyne followed by Lucentis-Dexamethasone triple therapy [within 2 hours]) reduces retreatment rates compared with Lucentis monotherapy while maintaining similar vision outcomes and an acceptable safety profile.

Study Overview

• Status: Completed
• Conditions: Macular Degeneration; Choroidal Neovascularization
• Intervention / Treatment: Drug: verteporfin; Drug: verteporfin; Drug: ranibizumab; Drug: dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
  • Ontario
    • London, Ontario, Canada
    • Toronto, Ontario, Canada
• United States
  • Alabama
    • Mobile, Alabama, United States
  • Arizona
    • Phoenix, Arizona, United States
    • Tucson, Arizona, United States
      • Retina Centers, PC
  • California
    • Beverly Hills, California, United States
    • Campbell, California, United States
    • Los Angeles, California, United States
    • Poway, California, United States
    • Sacramento, California, United States
    • Torrance, California, United States
  • Florida
    • Fort Myers, Florida, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Iowa
    • Davenport, Iowa, United States
  • Montana
    • Missoula, Montana, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Hampshire
    • Portsmouth, New Hampshire, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • West Mifflin, Pennsylvania, United States
  • Texas
    • Arlington, Texas, United States
    • Temple, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Treatment naive for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye except for laser treatment outside the subfoveal area
• Subfoveal CNV due to AMD
• CNV must be = or >50 % of the entire lesion
• All lesion composition types with a lesion greatest linear dimension (GLD) < 5400 microns (approximately = or <9 disc areas [DA])
• Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA score) of 25 - 73 letters (approximate Snellen equivalent of 20/40 - 20/320), inclusive

Exclusion Criteria:

• Subfoveal geographic atrophy or subfoveal fibrosis of the study eye
• Intraocular surgery within 3 months of enrollment
• Inability to attend the protocol-required visits
• Known allergies or hypersensitivity to any of the study treatments.
• Other systemic diseases or active uncontrolled infections that would make subject a poor medical risk
• Uncontrolled glaucoma, defined as (1)subject is on >1 glaucoma medication (includes combination treatments) or (2)subject has glaucoma that could lead to progressive visual field deterioration
• If subject has had a stroke within the last year

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1/4 Fluence Triple Therapy; Very low fluence Visudyne followed by intravitreal Lucentis-Dexamethasone triple therapy [within 2 hours] administered on Day 0, and then as required every 2 months thereafter	Drug: verteporfin; Reduced-fluence Visudyne (25 J/cm2, 300 mW/cm2, 83 seconds); Other Names: Visudyne; photodynamic therapy; Drug: verteporfin; Very-low fluence Visudyne (15 J/cm2, 180 mW/cm2, 83 seconds); Other Names: Visudyne; photodynamic therapy; Drug: ranibizumab; 0.5 mg intravitreal injection; Other Names: Lucentis; Drug: dexamethasone; 0.5 mg intravitreal injection
Experimental: 1/2 Fluence Triple Therapy; Reduced-fluence Visudyne followed by intravitreal Lucentis-Dexamethasone triple therapy [within 2 hours] administered on Day 0, and then as required every 2 months thereafter	Drug: verteporfin; Reduced-fluence Visudyne (25 J/cm2, 300 mW/cm2, 83 seconds); Other Names: Visudyne; photodynamic therapy; Drug: verteporfin; Very-low fluence Visudyne (15 J/cm2, 180 mW/cm2, 83 seconds); Other Names: Visudyne; photodynamic therapy; Drug: ranibizumab; 0.5 mg intravitreal injection; Other Names: Lucentis; Drug: dexamethasone; 0.5 mg intravitreal injection
Experimental: 1/2 Fluence Double Therapy; Reduced-fluence Visudyne followed by Lucentis double therapy [within 2 hours] administered on Day 0, and then as required every 2 months thereafter	Drug: verteporfin; Reduced-fluence Visudyne (25 J/cm2, 300 mW/cm2, 83 seconds); Other Names: Visudyne; photodynamic therapy; Drug: verteporfin; Very-low fluence Visudyne (15 J/cm2, 180 mW/cm2, 83 seconds); Other Names: Visudyne; photodynamic therapy; Drug: ranibizumab; 0.5 mg intravitreal injection; Other Names: Lucentis
Experimental: Ranibizumab; Lucentis monotherapy administered on Day 0, Month 1 and Month 2, and then as required monthly thereafter	Drug: ranibizumab; 0.5 mg intravitreal injection; Other Names: Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Retreatments (Day 0 Excluded)	Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment.	Month 1 to Month 12
Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart)	Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100	Baseline to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Retreatments (Day 0 Excluded)	Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment.	Month 1 to Month 24
Mean Change From Baseline in Study Eye Best-Corrected VA Score	Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100	Baseline to Month 24
Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline		Baseline to Month 12, Baseline to Month 24
Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline		Baseline to Month 12, Baseline to Month 24
Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline		Baseline to Month 12, Baseline to Month 24
Mean Change From Baseline in Central Retinal Thickness		Baseline to Month 12, Baseline to Month 24
Mean Change From Baseline in Lesion Size	Mean change from baseline in lesion size measured as greatest linear dimension (GLD) of the lesion	Baseline to Month 12, Baseline to Month 24

Collaborators and Investigators

• Sponsor: QLT Inc.
• Investigators: Study Director: Oscar Cuzzani, MD, QLT Inc.; Principal Investigator: Henry Hudson, MD, Retina Centers, PC; Principal Investigator: Allen Ho, MD, Retina Diagnostic & Treatment Associates, LLC; Study Chair: Andrew Strong, Ph.D, QLT Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: June 25, 2007
• First Submitted That Met QC Criteria: June 26, 2007
• First Posted (Estimate): June 27, 2007

Study Record Updates

• Last Update Posted (Estimate): June 2, 2011
• Last Update Submitted That Met QC Criteria: May 31, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: AMD; Photodynamic therapy; Choroidal neovascularization; Macular Degeneration; CNV; CNV Secondary to Age Related Macular Degeneration
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Retinal Degeneration; Retinal Diseases; Uveal Diseases; Choroid Diseases; Metaplasia; Macular Degeneration; Choroidal Neovascularization; Neovascularization, Pathologic; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Photosensitizing Agents; Dermatologic Agents; Dexamethasone; Ranibizumab; Verteporfin
• Other Study ID Numbers: BPD OCR 022